#!/usr/bin/env python3
"""
Build: Hypothalamus & Pituitary - Postgraduate IMED Presentation
"""

import json, subprocess, base64
from io import BytesIO
from pptx import Presentation
from pptx.util import Inches, Pt, Emu
from pptx.dml.color import RGBColor
from pptx.enum.text import PP_ALIGN, MSO_ANCHOR
from pptx.oxml.ns import qn
from lxml import etree

# ── Colour palette ──────────────────────────────────────────────
DEEP_BLUE    = RGBColor(0x1A, 0x3A, 0x6B)   # title bg / headers
TEAL         = RGBColor(0x00, 0x7B, 0x8A)   # accent
AMBER        = RGBColor(0xE8, 0x8C, 0x00)   # clinical highlight
WHITE        = RGBColor(0xFF, 0xFF, 0xFF)
LIGHT_GREY   = RGBColor(0xF2, 0xF4, 0xF8)
DARK_TEXT    = RGBColor(0x1C, 0x1C, 0x2E)
GREEN        = RGBColor(0x19, 0x7A, 0x3E)
RED          = RGBColor(0xC0, 0x39, 0x2B)

W = Inches(13.333)
H = Inches(7.5)

prs = Presentation()
prs.slide_width  = W
prs.slide_height = H
blank = prs.slide_layouts[6]

# ── Image downloader ─────────────────────────────────────────────
IMAGE_URLS = {
    "hp_org":    "https://cdn.orris.care/cdss_images/fc834bd4a357e8c725291d5c219224ffd2a39c3bb77a3081f5347b840c2e226e.png",
    "gh_signal": "https://cdn.orris.care/cdss_images/782a2aebbc7185a538262cd3dae5fde2b143ee24e95693ad82d23bc7eb3d1770.png",
    "anatomy":   "https://cdn.orris.care/cdss_images/afb5273aafe5273150313cba7dcafaa56fc35b8c6537fc711ad879bc2bb51c9a.png",
}

def fetch_images(urls_dict):
    url_list = list(urls_dict.values())
    result = json.loads(subprocess.check_output(
        ["python", "/tmp/skills/shared/scripts/fetch_images.py"] + url_list
    ))
    out = {}
    for key, url in urls_dict.items():
        for item in result:
            if item["url"] == url and item.get("base64"):
                raw = base64.b64decode(item["base64"].split(",",1)[-1])
                out[key] = BytesIO(raw)
    return out

imgs = fetch_images(IMAGE_URLS)

# ── Helpers ──────────────────────────────────────────────────────
def add_rect(slide, x, y, w, h, fill_rgb):
    shape = slide.shapes.add_shape(1, x, y, w, h)
    shape.fill.solid()
    shape.fill.fore_color.rgb = fill_rgb
    shape.line.fill.background()
    return shape

def add_tb(slide, text, x, y, w, h, size=18, bold=False, color=DARK_TEXT,
           align=PP_ALIGN.LEFT, wrap=True, italic=False):
    tb = slide.shapes.add_textbox(x, y, w, h)
    tf = tb.text_frame
    tf.word_wrap = wrap
    tf.margin_left  = 0
    tf.margin_right = 0
    tf.margin_top   = 0
    tf.margin_bottom= 0
    p = tf.paragraphs[0]
    p.alignment = align
    run = p.add_run()
    run.text = text
    run.font.size   = Pt(size)
    run.font.bold   = bold
    run.font.italic = italic
    run.font.color.rgb = color
    run.font.name   = "Calibri"
    return tb

def add_multiline_tb(slide, lines, x, y, w, h, size=16, color=DARK_TEXT,
                     line_space=1.15, wrap=True, bold_first=False):
    """lines = list of (text, bold, color_override)"""
    tb = slide.shapes.add_textbox(x, y, w, h)
    tf = tb.text_frame
    tf.word_wrap = wrap
    tf.margin_left   = Pt(4)
    tf.margin_right  = Pt(2)
    tf.margin_top    = Pt(2)
    tf.margin_bottom = Pt(2)
    for i, item in enumerate(lines):
        if isinstance(item, str):
            text, bold_, col_ = item, False, color
        else:
            text = item[0]
            bold_ = item[1] if len(item) > 1 else False
            col_  = item[2] if len(item) > 2 else color
        if i == 0:
            p = tf.paragraphs[0]
        else:
            p = tf.add_paragraph()
        p.space_before = Pt(2)
        run = p.add_run()
        run.text = text
        run.font.size  = Pt(size)
        run.font.bold  = bold_
        run.font.color.rgb = col_
        run.font.name  = "Calibri"
    return tb

def header_bar(slide, title, subtitle=None):
    add_rect(slide, 0, 0, W, Inches(1.15), DEEP_BLUE)
    add_tb(slide, title,
           Inches(0.35), Inches(0.12), Inches(12.0), Inches(0.65),
           size=30, bold=True, color=WHITE)
    if subtitle:
        add_tb(slide, subtitle,
               Inches(0.35), Inches(0.72), Inches(11), Inches(0.38),
               size=15, color=RGBColor(0xB8, 0xD4, 0xF5))

def footer(slide, text="Hypothalamus & Pituitary  |  Postgraduate Internal Medicine"):
    add_rect(slide, 0, Inches(7.2), W, Inches(0.3), DEEP_BLUE)
    add_tb(slide, text, Inches(0.3), Inches(7.21), Inches(11), Inches(0.28),
           size=9, color=WHITE)

def bullet_box(slide, items, x, y, w, h, size=15, head=None, head_color=TEAL,
               bullet="•  ", bg=None):
    if bg:
        add_rect(slide, x, y, w, h, bg)
    top = y
    if head:
        add_tb(slide, head, x+Inches(0.08), top+Inches(0.06), w-Inches(0.16),
               Inches(0.38), size=14, bold=True, color=head_color)
        top += Inches(0.42)
    tb = slide.shapes.add_textbox(x+Inches(0.12), top+Inches(0.04),
                                  w-Inches(0.24), h - (top-y) - Inches(0.08))
    tf = tb.text_frame
    tf.word_wrap = True
    tf.margin_left = Pt(2); tf.margin_right = Pt(2)
    tf.margin_top  = Pt(2); tf.margin_bottom = Pt(2)
    for i, item in enumerate(items):
        if isinstance(item, tuple):
            txt, bld = item
        else:
            txt, bld = item, False
        p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
        p.space_before = Pt(3)
        run = p.add_run()
        run.text = bullet + txt
        run.font.size  = Pt(size)
        run.font.bold  = bld
        run.font.color.rgb = DARK_TEXT
        run.font.name  = "Calibri"

def clinical_box(slide, title, points, x, y, w, h, size=13):
    add_rect(slide, x, y, w, h, RGBColor(0xFF, 0xF3, 0xCD))
    # amber left bar
    add_rect(slide, x, y, Inches(0.07), h, AMBER)
    add_tb(slide, f"⚕ {title}", x+Inches(0.12), y+Inches(0.06),
           w-Inches(0.2), Inches(0.35), size=13, bold=True, color=AMBER)
    tb = slide.shapes.add_textbox(x+Inches(0.12), y+Inches(0.38),
                                  w-Inches(0.2), h-Inches(0.44))
    tf = tb.text_frame; tf.word_wrap = True
    tf.margin_left = Pt(2); tf.margin_right = Pt(2)
    tf.margin_top = Pt(1); tf.margin_bottom = Pt(1)
    for i, pt in enumerate(points):
        p = tf.paragraphs[0] if i == 0 else tf.add_paragraph()
        p.space_before = Pt(2)
        run = p.add_run()
        run.text = "• " + pt
        run.font.size = Pt(size)
        run.font.color.rgb = RGBColor(0x5A, 0x3E, 0x00)
        run.font.name = "Calibri"

# ════════════════════════════════════════════════════════════════
# SLIDE 1 — TITLE
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, DEEP_BLUE)
# decorative teal stripe
add_rect(sl, 0, Inches(2.7), W, Inches(0.08), TEAL)
add_rect(sl, 0, Inches(5.4), W, Inches(0.08), TEAL)

add_tb(sl, "HYPOTHALAMUS & PITUITARY",
       Inches(1.0), Inches(1.2), Inches(11.3), Inches(1.1),
       size=44, bold=True, color=WHITE, align=PP_ALIGN.CENTER)
add_tb(sl, "Anatomy · Releasing Hormones · Growth Hormone Physiology · IGF-1",
       Inches(1.0), Inches(2.4), Inches(11.3), Inches(0.5),
       size=18, color=RGBColor(0xB8, 0xD4, 0xF5), align=PP_ALIGN.CENTER)
add_tb(sl, "Postgraduate Internal Medicine",
       Inches(1.0), Inches(2.9), Inches(11.3), Inches(0.45),
       size=16, color=TEAL, align=PP_ALIGN.CENTER, italic=True)
add_tb(sl, "Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics · Neuroanatomy through Clinical Cases (3rd Ed)",
       Inches(1.0), Inches(6.8), Inches(11.3), Inches(0.4),
       size=10, color=RGBColor(0x80, 0xA8, 0xD0), align=PP_ALIGN.CENTER, italic=True)

# ════════════════════════════════════════════════════════════════
# SLIDE 2 — OVERVIEW & LEARNING OBJECTIVES
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Learning Objectives", "What you will master in this session")

# Two columns
left_items = [
    ("Describe the embryology & anatomy of the hypothalamus and pituitary", False),
    ("List all major hypothalamic releasing / inhibiting hormones", False),
    ("Trace the hypothalamic-pituitary portal system", False),
    ("Explain anterior vs posterior pituitary differences", False),
    ("Outline GH secretion, regulation & signalling (JAK-STAT)", False),
    ("Describe IGF-1 synthesis, transport & tissue actions", False),
]
right_items = [
    ("Recognise clinical syndromes of GH excess (acromegaly/gigantism)", False),
    ("Recognise clinical syndromes of GH deficiency", False),
    ("Apply investigations: GH stimulation/suppression, IGF-1", False),
    ("Understand pharmacological targets (octreotide, pegvisomant)", False),
    ("Correlate pituitary anatomy with visual field defects", False),
    ("Integrate feedback loops for exam scenarios", False),
]
add_rect(sl, Inches(0.4), Inches(1.3), Inches(6.0), Inches(5.7), WHITE)
add_rect(sl, Inches(6.7), Inches(1.3), Inches(6.0), Inches(5.7), WHITE)

bullet_box(sl, left_items, Inches(0.4), Inches(1.3), Inches(6.0), Inches(5.7),
           size=14, head="By the end of this lecture you will:", head_color=TEAL)
bullet_box(sl, right_items, Inches(6.7), Inches(1.3), Inches(6.0), Inches(5.7),
           size=14, head="Clinical Correlations covered:", head_color=TEAL)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 3 — HYPOTHALAMUS ANATOMY
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Hypothalamus — Anatomy & Position",
           "Diencephalon · Floor & walls of 3rd ventricle")

# Image left
if "anatomy" in imgs:
    imgs["anatomy"].seek(0)
    sl.shapes.add_picture(imgs["anatomy"], Inches(0.3), Inches(1.3),
                          Inches(5.6), Inches(5.9))

# Text right
add_rect(sl, Inches(6.2), Inches(1.3), Inches(6.8), Inches(5.9), WHITE)
bullet_box(sl, [
    ("Part of the diencephalon, beneath the thalamus", False),
    ("Forms floor & lateral walls of the inferior 3rd ventricle", False),
    ("Separated from thalamus by the hypothalamic sulcus", False),
    ("Ventral landmarks: optic chiasm → tuber cinereum → mammillary bodies", False),
    ("Infundibulum (pituitary stalk) connects it to the pituitary", False),
    ("Contains several named nuclei: supraoptic (SON), paraventricular (PVN), arcuate (ARC), ventromedial, lateral, anterior & posterior", False),
    ("Central regulator of homeostasis (mnemonic HEAL):", False),
    ("  H – Homeostatic (hunger, thirst, temperature, circadian)", False),
    ("  E – Endocrine control via pituitary", False),
    ("  A – Autonomic control", False),
    ("  L – Limbic mechanisms", False),
], Inches(6.2), Inches(1.3), Inches(6.8), Inches(5.9), size=13,
   head="Key Anatomical Facts", head_color=TEAL)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 4 — PITUITARY ANATOMY & EMBRYOLOGY
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Pituitary Gland — Anatomy & Embryology",
           "Anterior (adenohypophysis) vs Posterior (neurohypophysis)")

# Top half: two boxes
add_rect(sl, Inches(0.3), Inches(1.3), Inches(6.2), Inches(2.8), WHITE)
add_rect(sl, Inches(6.7), Inches(1.3), Inches(6.3), Inches(2.8), WHITE)

bullet_box(sl, [
    ("Anterior pituitary = adenohypophysis", True),
    ("Embryology: oral ectoderm → Rathke's pouch invagination", False),
    ("Contains glandular secretory cells", False),
    ("Controlled by hypothalamus via portal blood (not direct innervation)", False),
    ("Hormones: GH, TSH, ACTH, FSH, LH, Prolactin", False),
    ("Intermediate lobe (pars intermedia) — rudimentary in adults", False),
], Inches(0.3), Inches(1.3), Inches(6.2), Inches(2.8), size=13,
   head="Anterior Pituitary", head_color=TEAL)

bullet_box(sl, [
    ("Posterior pituitary = neurohypophysis", True),
    ("Embryology: downward evagination of diencephalon floor", False),
    ("No glandular cells — contains axon terminals only", False),
    ("Cell bodies in SON & PVN nuclei of hypothalamus", False),
    ("Hormones stored & released: ADH (vasopressin) + Oxytocin", False),
    ("Direct neurosecretion into systemic circulation", False),
], Inches(6.7), Inches(1.3), Inches(6.3), Inches(2.8), size=13,
   head="Posterior Pituitary", head_color=DEEP_BLUE)

# Middle: relations table
add_rect(sl, Inches(0.3), Inches(4.25), Inches(12.7), Inches(0.35), DEEP_BLUE)
add_tb(sl, "  KEY ANATOMICAL RELATIONS — CLINICAL IMPORTANCE",
       Inches(0.3), Inches(4.25), Inches(12.7), Inches(0.35),
       size=12, bold=True, color=WHITE)

relations = [
    ("Superior", "Optic chiasm", "Bitemporal hemianopia — classic pituitary mass sign"),
    ("Lateral", "Cavernous sinus (CN III, IV, V1, V2, VI)", "Cavernous sinus syndrome"),
    ("Inferior", "Sphenoid sinus / sella turcica", "Trans-sphenoidal surgical access"),
    ("Posterior", "Basilar artery, pons", "Stroke risk with large lesions"),
]
col_x = [Inches(0.35), Inches(2.0), Inches(5.5), Inches(8.5)]
col_w = [Inches(1.6),  Inches(3.3), Inches(2.8), Inches(4.5)]
for ri, row in enumerate(relations):
    ry = Inches(4.65) + ri * Inches(0.58)
    bg = LIGHT_GREY if ri % 2 == 0 else WHITE
    add_rect(sl, Inches(0.3), ry, Inches(12.7), Inches(0.56), bg)
    for ci, cell in enumerate(row):
        add_tb(sl, cell, col_x[ci]+Inches(0.05), ry+Inches(0.05),
               col_w[ci]-Inches(0.1), Inches(0.46),
               size=12, bold=(ci==0))

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 5 — HYPOTHALAMIC-PITUITARY ORGANISATION (with image)
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Hypothalamic-Pituitary Organisation",
           "Portal system · Nucleus-specific hormone release")

# Image centre-left
if "hp_org" in imgs:
    imgs["hp_org"].seek(0)
    sl.shapes.add_picture(imgs["hp_org"], Inches(0.3), Inches(1.25),
                          Inches(5.2), Inches(5.85))

# Right: description
add_rect(sl, Inches(5.7), Inches(1.25), Inches(7.3), Inches(5.85), WHITE)
bullet_box(sl, [
    ("Hypothalamic neurons → median eminence → portal capillaries", False),
    ("Portal blood delivers releasing hormones to anterior pituitary", False),
    ("Anterior pituitary cells respond by secreting trophic hormones", False),
    ("Trophic hormones → target endocrine organs → feedback to both hypothalamus & pituitary", False),
    ("", False),
    ("SON & PVN nuclei → posterior pituitary via direct axonal transport", True),
    ("PVN & ARC nuclei → anterior pituitary via portal system", True),
    ("", False),
    ("Key: dopamine inhibits prolactin (tonically — loss of stalk = hyperprolactinaemia)", False),
    ("Key: somatostatin inhibits both GH and TSH", False),
], Inches(5.7), Inches(1.25), Inches(7.3), Inches(5.85), size=13,
   head="The Portal Connection", head_color=TEAL)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 6 — HYPOTHALAMIC RELEASING HORMONES TABLE
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Hypothalamic Releasing & Inhibiting Hormones",
           "Complete reference table — Goodman & Gilman, Table 46-1")

table_data = [
    ("GHRH", "Growth hormone-releasing hormone", "ARC nucleus", "↑ GH secretion", "IGF-1", TEAL),
    ("Somatostatin (SST)", "Somatotropin release-inhibiting hormone", "PVN & periventricular", "↓ GH  ↓ TSH", "—", RGBColor(0x6A,0x1B,0x9A)),
    ("Dopamine (DA)", "Prolactin inhibitory factor", "ARC / tuberoinfundibular", "↓ Prolactin (tonic)", "—", RGBColor(0x1B,0x5E,0x20)),
    ("TRH", "Thyrotropin-releasing hormone", "PVN", "↑ TSH  ↑ Prolactin", "Thyroid hormone", RGBColor(0x0D,0x47,0xA1)),
    ("CRH", "Corticotropin-releasing hormone", "PVN", "↑ ACTH", "Cortisol", RED),
    ("GnRH", "Gonadotropin-releasing hormone", "Preoptic area", "↑ LH  ↑ FSH", "Oestrogen / Testosterone", RGBColor(0x4A,0x14,0x86)),
    ("Oxytocin / ADH", "Posterior pituitary peptides", "SON & PVN", "Direct release (not portal)", "Kidney / uterus / breast", DEEP_BLUE),
]

# header row
hdr_x = [Inches(0.3), Inches(1.65), Inches(3.45), Inches(5.65), Inches(7.95), Inches(10.15)]
hdr_w = [Inches(1.3),  Inches(1.75), Inches(2.15), Inches(2.25), Inches(2.15), Inches(2.9)]
hdr_labels = ["Hormone", "Full Name", "Origin Nucleus", "Pituitary Effect", "Target Hormone", ""]
add_rect(sl, Inches(0.3), Inches(1.25), Inches(12.7), Inches(0.42), DEEP_BLUE)
for ci, lbl in enumerate(hdr_labels[:-1]):
    add_tb(sl, lbl, hdr_x[ci]+Inches(0.04), Inches(1.27), hdr_w[ci], Inches(0.38),
           size=12, bold=True, color=WHITE)

row_h = Inches(0.72)
for ri, row in enumerate(table_data):
    abb, full, nucleus, effect, target, accent = row
    ry = Inches(1.68) + ri * row_h
    bg = LIGHT_GREY if ri % 2 == 0 else WHITE
    add_rect(sl, Inches(0.3), ry, Inches(12.7), row_h, bg)
    add_rect(sl, Inches(0.3), ry, Inches(0.05), row_h, accent)
    texts = [abb, full, nucleus, effect, target]
    for ci, txt in enumerate(texts):
        bold_ = ci == 0
        add_tb(sl, txt, hdr_x[ci]+Inches(0.08), ry+Inches(0.06),
               hdr_w[ci]-Inches(0.12), row_h-Inches(0.1),
               size=11, bold=bold_, color=accent if ci==0 else DARK_TEXT,
               wrap=True)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 7 — GH PHYSIOLOGY: SECRETION & REGULATION
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Growth Hormone — Secretion & Regulation",
           "191 amino-acid peptide · Pulsatile · GHRH vs Somatostatin balance")

# 3-column layout
col_w = Inches(4.1)
cols = [Inches(0.3), Inches(4.55), Inches(8.8)]

boxes = [
    ("GH Stimulators", GREEN, [
        "GHRH (from ARC nucleus)",
        "Deep sleep (slow-wave, stage 3-4)",
        "Hypoglycaemia / fasting / exercise",
        "Amino acids (arginine, leucine)",
        "Oestrogens, testosterone",
        "Ghrelin (acylated — potent stimulus)",
        "α-adrenergic agonists, dopamine",
        "Stress (physical & psychological)",
    ]),
    ("GH Inhibitors", RED, [
        "Somatostatin (SRIH) — main brake",
        "IGF-1 (long-loop negative feedback)",
        "GH itself (short-loop feedback)",
        "Hyperglycaemia",
        "Free fatty acids",
        "β-adrenergic agonists",
        "Glucocorticoid excess",
        "Hypothyroidism",
    ]),
    ("Secretion Pattern", TEAL, [
        "Pulsatile: 3-5 pulses per day",
        "Peak secretion at night (slow-wave sleep)",
        "Liver is primary target → IGF-1",
        "Half-life of GH ~15-20 min",
        "IGF-1 has longer half-life (~15-20 h)",
        "98% of IGF-1 bound to IGFBP-3 + ALS",
        "IGF-1 is the best single marker of GH status",
        "Pulsatility makes random GH unreliable",
    ]),
]
for ci, (head, col, items) in enumerate(boxes):
    add_rect(sl, cols[ci], Inches(1.25), col_w, Inches(5.85), WHITE)
    add_rect(sl, cols[ci], Inches(1.25), col_w, Inches(0.38), col)
    add_tb(sl, head, cols[ci]+Inches(0.1), Inches(1.28), col_w-Inches(0.2), Inches(0.32),
           size=13, bold=True, color=WHITE)
    bullet_box(sl, items, cols[ci], Inches(1.63), col_w, Inches(4.85), size=12)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 8 — GH RECEPTOR SIGNALLING (with image)
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "GH Receptor Signalling — JAK-STAT Pathway",
           "Cytokine superfamily receptor · Downstream effectors · Drug targets")

if "gh_signal" in imgs:
    imgs["gh_signal"].seek(0)
    sl.shapes.add_picture(imgs["gh_signal"], Inches(0.3), Inches(1.25),
                          Inches(5.6), Inches(5.8))

add_rect(sl, Inches(6.1), Inches(1.25), Inches(6.95), Inches(5.8), WHITE)
bullet_box(sl, [
    ("GH binds GH receptor (GHR) — forms 1:2 GH-GHR ternary complex", True),
    ("GHR is a cytokine superfamily receptor (no intrinsic kinase)", False),
    ("Dimerisation → recruitment & auto-phosphorylation of JAK2", False),
    ("JAK2 phosphorylates STAT5 → nucleus → IGF-1 gene expression", False),
    ("Also activates: MAPK (SHC pathway) → mitogenic effects", False),
    ("IRS-1 pathway → glucose transporter expression", False),
    ("", False),
    ("Key metabolic effects of GH:", True),
    ("  ↑ Lipolysis (anti-insulin in adipose)", False),
    ("  ↑ Gluconeogenesis (diabetogenic)", False),
    ("  ↑ Protein synthesis (anabolic)", False),
    ("  Most growth-promoting effects → INDIRECT via IGF-1", False),
    ("", False),
    ("Pharmacological target — Pegvisomant:", True),
    ("  Mutant GH analogue → blocks GHR dimerisation → no JAK2 activation", False),
    ("  Used in acromegaly refractory to somatostatin analogues", False),
], Inches(6.1), Inches(1.25), Inches(6.95), Inches(5.8), size=12,
   head="Signalling Cascade", head_color=TEAL)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 9 — IGF-1 PHYSIOLOGY
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "IGF-1 (Insulin-like Growth Factor-1)",
           "Somatomedin C · GH mediator · Liver-derived · Autocrine/Paracrine actions")

# 4 panels
panel_cfg = [
    (Inches(0.3),  Inches(1.25), Inches(6.2), Inches(2.75), "Structure & Source", TEAL, [
        "70 amino acid single-chain peptide",
        "Structural similarity to insulin (hence 'insulin-like')",
        "Synthesised primarily in the liver (GH-dependent)",
        "Also produced locally in most tissues (autocrine/paracrine)",
        "GH-independent IGF-1 production in early foetal development",
    ]),
    (Inches(6.7),  Inches(1.25), Inches(6.3), Inches(2.75), "Transport & Binding Proteins", DEEP_BLUE, [
        "98% circulates bound to IGF binding proteins (IGFBPs)",
        "IGFBP-3 + Acid-Labile Subunit (ALS): forms ternary complex",
        "Half-life extended from minutes to ~15-20 hours",
        "IGFBP-3 itself is GH-dependent — used as IGF-1 status marker",
        "Free IGF-1 (<2%) is biologically active",
    ]),
    (Inches(0.3),  Inches(4.15), Inches(6.2), Inches(2.95), "Tissue Actions", GREEN, [
        "Bone: stimulates chondrocyte proliferation → longitudinal growth",
        "Muscle: protein synthesis, satellite cell activation, anti-apoptotic",
        "Liver: anti-apoptotic, metabolic regulation",
        "Kidney: ↑ glomerular filtration rate",
        "Adipose: preadipocyte differentiation",
        "CNS: neuronal survival and differentiation",
    ]),
    (Inches(6.7),  Inches(4.15), Inches(6.3), Inches(2.95), "IGF-1 Receptor Signalling", AMBER, [
        "IGF-1R: receptor tyrosine kinase (α2β2 tetramer)",
        "Activates PI3K/AKT → cell survival & growth",
        "Activates MAPK/ERK → proliferation",
        "Overlaps with insulin signalling → hypoglycaemia risk with excess",
        "Key growth proof: biallelic IGF1 gene mutations → severe growth retardation unresponsive to GH but responsive to rh-IGF-1",
    ]),
]

for (px, py, pw, ph, ptitle, pcol, pitems) in panel_cfg:
    add_rect(sl, px, py, pw, ph, WHITE)
    add_rect(sl, px, py, pw, Inches(0.37), pcol)
    add_tb(sl, ptitle, px+Inches(0.08), py+Inches(0.04), pw-Inches(0.16), Inches(0.29),
           size=13, bold=True, color=WHITE)
    bullet_box(sl, pitems, px, py+Inches(0.37), pw, ph-Inches(0.37), size=11)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 10 — GH EXCESS: ACROMEGALY & GIGANTISM
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "GH Excess — Gigantism & Acromegaly",
           "Somatotrope adenoma · Pre-epiphyseal vs Post-epiphyseal fusion")

# Left: pathophysiology
add_rect(sl, Inches(0.3), Inches(1.25), Inches(6.1), Inches(5.85), WHITE)
bullet_box(sl, [
    ("Cause: somatotrope adenoma (>95%); rare: ectopic GHRH", True),
    ("Pre-pubertal (open epiphyses) → GIGANTISM", False),
    ("Post-pubertal (fused epiphyses) → ACROMEGALY", False),
    ("", False),
    ("Cardinal features of acromegaly:", True),
    ("  Acral enlargement: hands, feet, jaw (prognathism)", False),
    ("  Coarsening facial features, macroglossia", False),
    ("  Skin: hyperhidrosis, oily, skin tags", False),
    ("  Organomegaly: cardiomegaly, hepatomegaly", False),
    ("  Arthropathy, carpal tunnel syndrome", False),
    ("  Hypertension, LVH — major cause of mortality", False),
    ("  Diabetes mellitus (GH diabetogenic effect)", False),
    ("  Sleep apnoea (upper airway soft tissue)", False),
    ("  Visual field defects if tumour compresses chiasm", False),
], Inches(0.3), Inches(1.25), Inches(6.1), Inches(5.85), size=12,
   head="Pathophysiology & Features", head_color=RED)

# Right top: investigations
add_rect(sl, Inches(6.6), Inches(1.25), Inches(6.4), Inches(2.9), WHITE)
bullet_box(sl, [
    ("Screening: serum IGF-1 (age & sex-matched)", False),
    ("Confirmation: Oral Glucose Tolerance Test (OGTT)", False),
    ("  — Normal: GH suppresses to <0.4 μg/L at 2 h", False),
    ("  — Acromegaly: GH fails to suppress (paradoxical ↑)", False),
    ("MRI pituitary (gadolinium) — macroadenoma >1 cm usually", False),
    ("Screen for co-secretion: prolactin, TSH, alpha-subunit", False),
], Inches(6.6), Inches(1.25), Inches(6.4), Inches(2.9), size=12,
   head="Investigations", head_color=TEAL)

# Right bottom: treatment
add_rect(sl, Inches(6.6), Inches(4.3), Inches(6.4), Inches(2.8), WHITE)
bullet_box(sl, [
    ("Surgery: trans-sphenoidal resection (1st line)", True),
    ("Medical therapy:", False),
    ("  Somatostatin analogues (octreotide, lanreotide)", False),
    ("  Dopamine agonist (cabergoline) — modest effect", False),
    ("  GHR antagonist: pegvisomant (blocks GHR dimerisation)", False),
    ("Radiotherapy: adjunct for persistent disease", False),
    ("Aim: IGF-1 normalisation + GH <1 μg/L on OGTT", False),
], Inches(6.6), Inches(4.3), Inches(6.4), Inches(2.8), size=12,
   head="Treatment Ladder", head_color=AMBER)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 11 — GH DEFICIENCY
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "GH Deficiency (GHD)",
           "Children vs Adults · Diagnosis · IGF-1 Deficiency States")

add_rect(sl, Inches(0.3), Inches(1.25), Inches(6.1), Inches(5.85), WHITE)
bullet_box(sl, [
    ("Childhood GHD:", True),
    ("  Short stature (height velocity < 4-5 cm/yr)", False),
    ("  Delayed bone age", False),
    ("  Truncal adiposity, cherubic face", False),
    ("  Micropenis in males", False),
    ("  Causes: pituitary aplasia/hypoplasia, craniopharyngioma, irradiation", False),
    ("", False),
    ("Adult GHD:", True),
    ("  ↑ Fat mass (central), ↓ muscle mass, ↓ exercise capacity", False),
    ("  Dyslipidaemia: ↑ LDL, ↓ HDL", False),
    ("  Reduced bone mineral density", False),
    ("  Fatigue, impaired quality of life, depression", False),
    ("  ↑ Cardiovascular risk", False),
    ("  Causes: pituitary adenoma / surgery / irradiation", False),
], Inches(0.3), Inches(1.25), Inches(6.1), Inches(5.85), size=12,
   head="Clinical Features", head_color=DEEP_BLUE)

add_rect(sl, Inches(6.6), Inches(1.25), Inches(6.4), Inches(2.85), WHITE)
bullet_box(sl, [
    ("IGF-1 low for age/sex — screening test", False),
    ("GH stimulation tests (insulin tolerance test / glucagon):", False),
    ("  Peak GH < 3 μg/L = severe GHD", False),
    ("  Peak GH 3-7 μg/L = partial GHD (context-dependent)", False),
    ("IGFBP-3 — complements IGF-1, especially in children < 3 yrs", False),
    ("MRI: pituitary/hypothalamic pathology", False),
], Inches(6.6), Inches(1.25), Inches(6.4), Inches(2.85), size=12,
   head="Investigations", head_color=TEAL)

add_rect(sl, Inches(6.6), Inches(4.25), Inches(6.4), Inches(2.85), WHITE)
bullet_box(sl, [
    ("Primary IGF-1 deficiency (Laron syndrome):", True),
    ("  GH receptor mutations → ↑↑ GH + ↓ IGF-1", False),
    ("  Phenotype similar to GHD — unresponsive to GH", False),
    ("  Treat with recombinant human IGF-1 (mecasermin)", False),
    ("", False),
    ("Treatment of GHD: recombinant hGH (somatropin)", False),
    ("Titrate to IGF-1 in mid-normal range for age", False),
], Inches(6.6), Inches(4.25), Inches(6.4), Inches(2.85), size=12,
   head="Laron Syndrome & Treatment", head_color=AMBER)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 12 — CLINICAL CORRELATIONS SUMMARY
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Clinical Correlations & Exam Pearls",
           "High-yield IMED scenarios")

cases = [
    ("Bitemporal Hemianopia",
     ["Pituitary macroadenoma compresses optic chiasm",
      "Classic: loss of temporal fields bilaterally",
      "Urgent investigation: MRI pituitary + formal perimetry",
      "Stalk compression → hyperprolactinaemia (dopamine interruption)"]),
    ("Acromegaly Diagnosis Trap",
     ["Random GH is unreliable — always use OGTT",
      "IGF-1 correlates best with disease activity",
      "GH co-secretion with TSH → thyrotoxicosis + acromegaly",
      "Skin tags + colonic polyps → screen with colonoscopy"]),
    ("Empty Sella Syndrome",
     ["CSF herniates through diaphragma sellae → flattens pituitary",
      "Usually incidental; pituitary function often preserved",
      "Secondary: post-surgery, apoplexy, Sheehan's syndrome",
      "Investigate all pituitary axes before assuming benign"]),
    ("Pituitary Apoplexy",
     ["Haemorrhage/infarction into pituitary adenoma",
      "Sudden headache + ophthalmoplegia + visual loss",
      "Emergency: IV glucocorticoids (adrenal crisis risk)",
      "MRI confirms; neurosurgical opinion urgently"]),
    ("Sheehan's Syndrome",
     ["Postpartum pituitary infarction — obstetric haemorrhage",
      "Failure to lactate is first clue",
      "Presents months–years later: panhypopituitarism",
      "Diagnose: all axes affected; MRI shows empty sella"]),
    ("Craniopharyngioma",
     ["Most common pituitary region tumour in children",
      "Calcified suprasellar mass on CT",
      "GHD first, then panhypopituitarism",
      "Diabetes insipidus common (hypothalamic involvement)"]),
]

px_starts = [Inches(0.3), Inches(4.55), Inches(8.8)]
py_starts = [Inches(1.25), Inches(4.2)]
pw = Inches(4.1); ph = Inches(2.7)
for i, (title, pts) in enumerate(cases):
    col = i % 3; row = i // 3
    cx = px_starts[col]; cy = py_starts[row]
    clinical_box(sl, title, pts, cx, cy, pw, ph, size=11)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 13 — PHARMACOLOGY OF H-P AXIS
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Pharmacology of the Hypothalamic-Pituitary Axis",
           "Therapeutic and diagnostic agents — mechanisms, indications, key notes")

drug_table = [
    ("Octreotide / Lanreotide", "Somatostatin analogue", "Inhibit GH secretion from somatotrope; ↓ portal blood flow", "Acromegaly; carcinoid; VIPoma; TSH-oma", "Gallstones; diarrhoea; ↓ insulin → hyperglycaemia"),
    ("Pegvisomant", "GH receptor antagonist", "Blocks GHR dimerisation → no JAK2 activation → ↓ IGF-1", "Acromegaly refractory to SSA", "↑ Liver enzymes; monitor IGF-1; GH levels rise (not a marker)"),
    ("Cabergoline", "D2 agonist (dopaminergic)", "Suppresses GH and prolactin secretion", "Prolactinoma (1st line); some acromegaly", "Nausea; valvulopathy (high dose); impulse control"),
    ("Somatropin (rh-GH)", "Recombinant GH", "Replaces endogenous GH; induces hepatic IGF-1", "GHD (child/adult); Turner; Prader-Willi; SGA", "Intracranial HTN; slipped capital femoral epiphysis; insulin resistance"),
    ("Mecasermin (rh-IGF-1)", "Recombinant IGF-1", "Bypasses GH axis — direct IGF-1 receptor agonism", "Laron syndrome; primary IGF-1 deficiency", "Hypoglycaemia; lipohypertrophy at injection sites"),
    ("Octreotide (GH stimulation test)", "Diagnostic (suppression)", "Oral glucose suppresses GH in normals; fails in acromegaly", "OGTT-GH suppression test", "Perform after 10h fast; measure GH at 0,30,60,90,120 min"),
]

hdr_cols = ["Drug", "Class", "Mechanism", "Indication", "Key Side-effects / Notes"]
col_x2 = [Inches(0.3), Inches(2.3), Inches(3.85), Inches(6.7), Inches(9.4)]
col_w2 = [Inches(1.95), Inches(1.5), Inches(2.8),  Inches(2.65), Inches(3.6)]

add_rect(sl, Inches(0.3), Inches(1.25), Inches(12.7), Inches(0.42), DEEP_BLUE)
for ci, lbl in enumerate(hdr_cols):
    add_tb(sl, lbl, col_x2[ci]+Inches(0.05), Inches(1.27), col_w2[ci], Inches(0.38),
           size=11, bold=True, color=WHITE)

for ri, row in enumerate(drug_table):
    ry = Inches(1.68) + ri * Inches(0.92)
    bg = LIGHT_GREY if ri % 2 == 0 else WHITE
    add_rect(sl, Inches(0.3), ry, Inches(12.7), Inches(0.9), bg)
    for ci, cell in enumerate(row):
        add_tb(sl, cell, col_x2[ci]+Inches(0.06), ry+Inches(0.04),
               col_w2[ci]-Inches(0.1), Inches(0.84),
               size=10, bold=(ci==0), wrap=True,
               color=TEAL if ci==0 else DARK_TEXT)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 14 — FEEDBACK LOOPS & INTEGRATION
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, LIGHT_GREY)
header_bar(sl, "Feedback Regulation — GH/IGF-1 Axis",
           "Long-loop, short-loop & ultrashort feedback mechanisms")

# Flow diagram using shapes
def flow_box(slide, text, x, y, w, h, fill, text_col=WHITE, size=13, bold=True):
    add_rect(slide, x, y, w, h, fill)
    add_tb(slide, text, x+Inches(0.06), y+Inches(0.06),
           w-Inches(0.12), h-Inches(0.12),
           size=size, bold=bold, color=text_col, align=PP_ALIGN.CENTER, wrap=True)

def arrow(slide, x1, y1, x2, y2):
    # Draw using a narrow rectangle as arrow line
    from pptx.util import Emu
    import math
    # Simple horizontal or vertical arrows using shapes
    if abs(y2-y1) < abs(x2-x1):
        # horizontal
        mid_y = (y1+y2)/2
        w_ = abs(x2-x1)
        x_ = min(x1,x2)
        add_rect(slide, x_, mid_y-Inches(0.02), w_, Inches(0.04), DARK_TEXT)
    else:
        # vertical
        mid_x = (x1+x2)/2
        h_ = abs(y2-y1)
        y_ = min(y1,y2)
        add_rect(slide, mid_x-Inches(0.02), y_, Inches(0.04), h_, DARK_TEXT)

# GH-IGF-1 axis flow diagram
bw = Inches(2.6); bh = Inches(0.55)
cx = Inches(5.3)  # centre x

flow_box(sl, "Hypothalamus: GHRH ↑ / Somatostatin ↓",
         Inches(3.5), Inches(1.3), Inches(6.2), bh, DEEP_BLUE)
arrow(sl, cx+Inches(1.1), Inches(1.85), cx+Inches(1.1), Inches(2.2))
flow_box(sl, "Anterior Pituitary Somatotrope → GH",
         Inches(3.5), Inches(2.2), Inches(6.2), bh, TEAL)
arrow(sl, cx+Inches(1.1), Inches(2.75), cx+Inches(1.1), Inches(3.1))
flow_box(sl, "Liver + Peripheral Tissues → IGF-1",
         Inches(3.5), Inches(3.1), Inches(6.2), bh, GREEN)
arrow(sl, cx+Inches(1.1), Inches(3.65), cx+Inches(1.1), Inches(4.0))
flow_box(sl, "Target Tissues: Bone · Muscle · Kidney · Adipose",
         Inches(3.5), Inches(4.0), Inches(6.2), bh, RGBColor(0x2E,0x7D,0x32))

# Feedback arrows (text boxes)
add_tb(sl, "⬅ Long-loop feedback: IGF-1 inhibits Hypothalamus & Pituitary",
       Inches(0.3), Inches(3.1), Inches(3.0), Inches(0.7),
       size=11, color=RED, italic=True, wrap=True)
add_tb(sl, "⬅ Short-loop feedback: GH inhibits its own release from Hypothalamus",
       Inches(0.3), Inches(2.2), Inches(3.0), Inches(0.7),
       size=11, color=RED, italic=True, wrap=True)
add_tb(sl, "⬅ Ultra-short: GHRH & SST autoregulation",
       Inches(0.3), Inches(1.3), Inches(3.0), Inches(0.55),
       size=11, color=RED, italic=True, wrap=True)

# Right side: key points
add_rect(sl, Inches(9.9), Inches(1.3), Inches(3.15), Inches(5.9), WHITE)
bullet_box(sl, [
    ("Negative feedback is the key principle on all pituitary axes", False),
    ("IGF-1 → both hypothalamus (↑SST, ↓GHRH) and pituitary (direct)", False),
    ("GH has anti-insulin actions → poor metabolic control → ↑SST", False),
    ("Sleep deprivation → blunted nocturnal GH pulse", False),
    ("Obesity → ↓ amplitude of GH pulses (SST ↑)", False),
    ("In starvation: GH ↑↑ but IGF-1 ↓ (hepatic resistance)", False),
    ("Exam trap: ↑ GH + ↓ IGF-1 = starvation/liver disease", False),
    ("Not GH excess!", False),
], Inches(9.9), Inches(1.3), Inches(3.15), Inches(5.9), size=12,
   head="Key Integration Points", head_color=TEAL)

footer(sl)

# ════════════════════════════════════════════════════════════════
# SLIDE 15 — SUMMARY & EXAM MNEMONICS
# ════════════════════════════════════════════════════════════════
sl = prs.slides.add_slide(blank)
add_rect(sl, 0, 0, W, H, DEEP_BLUE)
add_rect(sl, 0, Inches(1.1), W, Inches(0.05), TEAL)
add_rect(sl, 0, Inches(6.9), W, Inches(0.05), TEAL)

add_tb(sl, "Summary & Exam High-Yield Mnemonics",
       Inches(0.5), Inches(0.15), Inches(12.3), Inches(0.85),
       size=30, bold=True, color=WHITE)

mnems = [
    ("HEAL", "Hypothalamus functions:\nHomeostasis · Endocrine · Autonomic · Limbic"),
    ("GH UP", "GH stimulators:\nGhrelin/GHRH · Hypoglycaemia · Unfit (exercise) · Puberty/Oestrogen"),
    ("IGF-1 Triple Rule", "1) Best single GH-status marker\n2) Normal = active disease excluded\n3) ↑ GH + ↓ IGF-1 = not acromegaly (starvation/liver)"),
    ("OGTT Flip", "Normal: GH suppresses below 0.4 μg/L\nAcromegaly: GH does NOT suppress (may paradoxically rise)"),
    ("Pituitary Neighbours", "Superior = Chiasm (vision)\nLateral = Cavernous sinus (CN III,IV,VI)\nInferior = Sphenoid (surgery)"),
    ("3 Ps of Acromegaly", "Prognathism · Perspiration (hyperhidrosis) · Polyps (colonic screening)"),
]

cols2 = [Inches(0.4), Inches(4.55), Inches(8.7)]
rh = Inches(2.6)
for i, (title, body) in enumerate(mnems):
    col = i % 3; row = i // 3
    cx_ = cols2[col]; cy_ = Inches(1.25) + row * rh
    add_rect(sl, cx_, cy_, Inches(3.9), rh-Inches(0.1), RGBColor(0x12,0x28,0x4E))
    add_rect(sl, cx_, cy_, Inches(3.9), Inches(0.42), TEAL)
    add_tb(sl, title, cx_+Inches(0.08), cy_+Inches(0.05),
           Inches(3.74), Inches(0.32), size=14, bold=True, color=WHITE)
    add_tb(sl, body, cx_+Inches(0.1), cy_+Inches(0.46),
           Inches(3.7), rh-Inches(0.62),
           size=12, color=RGBColor(0xD0,0xE8,0xFF), wrap=True)

add_tb(sl, "Sources: Goodman & Gilman's Pharmacological Basis of Therapeutics (14e)  |  Neuroanatomy through Clinical Cases (3rd Ed, Blumenfeld)  |  Adams & Victor's Principles of Neurology (12th Ed)",
       Inches(0.4), Inches(7.05), Inches(12.5), Inches(0.35),
       size=9, color=RGBColor(0x70,0x98,0xC0), italic=True)

# Save
out_path = "/tmp/workspace/hypothalamus-pituitary-pptx/Hypothalamus_Pituitary_IMED.pptx"
buf = BytesIO()
prs.save(buf)
with open(out_path, "wb") as f:
    f.write(buf.getvalue())
print(f"Saved: {out_path}")
print(f"Slides: {len(prs.slides)}")