Hypopituitarism
Undersecretion of pituitary hormones due to:- Nonsecreting pituitary adenoma, craniopharyngioma- Sheehan syndrome – ischemic infarct of pituitary following postpartum bleeding; pregnancy-induced pituitary growth → ↑ susceptibility to hypoperfusion. Usually presents with failure to lactate, absent menstruation, cold intolerance.- Empty sella syndrome – atrophy or compression of pituitary (which lies in the sella turcica), often idiopathic, common in obese women; associated with idiopathic intracranial hypertension.- Pituitary apoplexy – sudden hemorrhage of pituitary gland, often in the presence of an existing pituitary adenoma. Usually presents with sudden onset severe headache, visual impairment (eg, bitemporal hemianopia, diplopia due to CN III palsy), and features of hypopituitarism.- Brain injury- Radiation Treatment: hormone replacement therapy (corticosteroids, thyroxine, sex steroids, human growth hormone)
Thyroid development
Thyroid diverticulum arises from floor of primitive pharynx and descends into neck. - Connected to tongue by thyroglossal duct, which normally disappears but may persist as cysts or the pyramidal lobe of thyroid. - Foramen cecum is normal remnant of thyroglossal duct. Most common ectopic thyroid tissue site is the tongue (lingual thyroid). Removal may result in hypothyroidism if it is the only thyroid tissue present. Thyroglossal duct cyst presents as an anterior midline neck mass that moves with swallowing or protrusion of the tongue (vs persistent cervical sinus leading to brachial cleft cyst in lateral neck). Thyroid follicular cells are derived from endoderm. Parafollicular cells (aka, C cells, produce calcitonin) are derived from neural crest.
Anterior pituitary (adenohypophysis)
Secretes FSH, LH, ACTH, TSH, PRL, GH, and β-endorphin. - Melanotropin (MSH) secreted from intermediate lobe of pituitary. - Basophils: FSH, LH, ACTH, TSH- Acidophils: GH, PRL - Derived from oral ectoderm (Rathke pouch). α subunit: hormone subunit common to TSH, LH, FSH, and hCGβ subunit: determines hormone specificity ACTH, MSH, and β-endorphin are derivatives of proopiomelanocortin (POMC).
Posterior pituitary (neurohypophysis)
Stores and releases vasopressin (antidiuretic hormone, or ADH) and oxytocin, both made in the hypothalamus.- ADH is made in the supraoptic nuclei.- Oxytocin is made in the paraventricular nuclei. - Transported to posterior pituitary via neurophysins (carrier proteins). - Derived from neuroectoderm (vs adenohypophysis from oral ectoderm)
Endocrine pancreas cell types
Islets of Langerhans are collections of α, β, and δ endocrine cells. Islets arise from pancreatic buds. α = glucagon (peripheral)β = insulin (central)δ = somatostatin (interspersed)
Insulin
Synthesis: Preproinsulin (synthesized in RER) → cleavage of "presignal" → proinsulin (stored in secretory granules) → cleavage of proinsulin → exocytosis of insulin and C-peptide equally. Function: Binds insulin receptors (tyrosine kinase activity), inducing glucose uptake (carrier-mediated transport) into insulin-dependent tissue and gene transcription. - Tyrosine phosphorylation → Phosphoinositide-3 kinase pathway → GLUT4 expression, glycogen, lipid, protein synthesis- Tyrosine phosphorylation → RAS/MAP kinase pathway → cell growth, DNA synthesis Anabolic effects of insulin: ↑ glucose transport in skeletal muscle and adipose tissue↑ glycogen, triglyceride, protein synthesis↑ Na+ retention (kidneys)↑ cellular uptake of K+ and amino acids↓ glucagon release- Unlike glucose, insulin does not cross placenta. Insulin-dependent glucose transporters:- GLUT-4: adipose tissue, striated muscle (exercise can also ↑ GLUT-4 expression)Insulin-independent transporters:- GLUT-1: RBCs, brain, cornea, placenta- GLUT-2 (bidirectional): β islet cells, liver, kidney, small intestine- GLUT-3: brain, placenta- GLUT-5 (fructose): spermatocytes, GI tract- SGLT1/SGLT2 (Na+-glucose cotransporters): kidney, small intestine
Hypothalamic-pituitary hormones
CRH: ↑ ACTH, MSH, β-endorphin- ↓ in chronic exogenous steroid use Dopamine: ↓ prolactin, TSH- Dopamine antagonists (eg, antipsychotics) can cause galactorrhea due to hyperprolactinemia GHRH: ↑ GH- Analog (tesamorelin) used to treat HIV-associated lipodystrophy GnRH: ↑ FSH, LH- Suppressed by hyperprolactinemia- Tonic GnRH suppresses HPG axis- Pulsatile GnRH leads to puberty, fertility MSH: ↑ melanogenesis by melanocytes- Causes hyperpigmentation in Cushing disease, as MSH and ACTH share the same precursor molecule, proopiomelanocortin. Prolactin: ↓ GnRH- Pituitary prolactinoma → amenorrhea, osteoporosis, hypogonadism, galactorrhea Somatostatin: ↓ GH, TSH TRH: ↑ TSH, prolactin- ↑ TSH (eg, in 1°/2° hypothyroidism) may increase prolactin secretion → galactorrhea
Growth hormone (somatotropin)
Secreted by anterior pituitary. Function: Stimulates linear growth and muscle mass through IGF-1 (somatomedin C) secretion by liver. ↑ insulin resistance (diabetogenic).- IGF-1 (somatomedin) increases synthesis of cartilage (chondrogenesis) Regulation: Released in pulses in response to growth-hormone-releasing hormone (GHRH). - Secretion ↑: exercise, deep sleep, puberty, hypoglycemia, ghrelin, amino-acids (eg, arginine). - Secretion ↓: glucose and somatostatin release via negative feedback by somatomedin. Excess secretion of GH (eg, pituitary adenoma) may cause acromegaly (adults) or gigantism (children). Treat with somatostatin anologs (eg, octreotide) or surgery.
Ghrelin
Stimulates hunger (orexigenic effect) and GH release (via GH secretagogue receptor). - Activated neuropeptide Y (orexigenic) Produced by stomach. Sleep deprivation or Prader-Willi syndrome → ↑ ghrelin production. Acts via lateral area of hypothalamus to ↑ appetite (hunger center).
Leptin
Satiety hormone. Produced by adipose tissue.- Decreases hypothalamic neuropeptide Y, which is a potent activator of feeding (orexigenic). Mutation of leptin gene → congenital obesity. Sleep deprivation or starvation → ↓ leptin production. Acts via ventromedial area of hypothalamus to ↓ appetite (satiety center).
Endocannabinoids
Act at cannabinoid receptors in hypothalamus and nucleus accumbens, two key brain areas for the homeostatic and hedonic control of food intake. ↑ appetite
17α-hydroxylase deficiency
↑ Mineralocorticoids↓ Cortisol↓ Sex hormones↑ BP↓ K+Labs: ↓ androstenedione Presentation: - XY: ambiguous genitalia, undescended testes- XX: lacks 2° sexual development All congenital adrenal enzyme deficiencies are characterized by skin hyperpigmentation (due to ↑ MSH production, which is coproduced and secreted with ACTH) and bilateral adrenal gland enlargement (due to ↑ ACTH stimulation).
21-hydroxylase deficiency
↓ Mineralcorticoids↓ Cortisol↑ Sex hormones↓ BP↑ K+ Labs: ↑ renin activity, ↑ 17-hydroxyprogesterone Presentation: - Most common- Presents in infancy (salt wasting) or in childhood (precocious puberty)- XX: virilization All congenital adrenal enzyme deficiencies are characterized by skin hyperpigmentation (due to ↑ MSH production, which is coproduced and secreted with ACTH) and bilateral adrenal gland enlargement (due to ↑ ACTH stimulation).
11β-hydroxylase deficiency
↓ Aldosterone↑ 11-deoxycorticosterone (results in ↑ BP)↓ Cortisol↑ Sex hormones↑ BP↓ K+ Labs: ↓ renin activity Presentation: - XX: virilization All congenital adrenal enzyme deficiencies are characterized by skin hyperpigmentation (due to ↑ MSH production, which is coproduced and secreted with ACTH) and bilateral adrenal gland enlargement (due to ↑ ACTH stimulation).
Cortisol
Source: Adrenal zona fasciculata. Bound to corticosteroid-binding globulin. Function: ↑ Appetite↑ Blood pressure- Upregulates α1 receptors on arterioles → ↑ sensitivity to norepinephrine and epinephrine (permissive action)- At high concentrations, can bind to mineralocorticoid (aldosterone) receptors↑ Insulin resistance (diabetogenic)↑ Gluconeogenesis, lipolysis, proteolysis↓ Fibroblast activity (poor wound healing, ↓ collagen synthesis, ↑ straie)↓ Inflammatory and immune responses: - Inhibits production of leukotrienes and prostaglandins- Inhibits WBC adhesion → neutrophilia- Blocks histamine release from mast cells- Eosinopenia, lymphopenia- Blocks IL-2 production↓ Bone formation (↓ osteoblast activity) Exogenous corticosteroids can cause reactivation of TB and candidiasis (blocks IL-2 production)
Calcium homeostasis
Plasma Ca2+ consists in three forms:- Ionized/free (~45%, active form)- Bound to albumin (~40%)- Bound to anions (~15%) ↑ in pH → ↑ affinity of albumin (↑ negative charge) to bind Ca2+ → hypocalcemia (eg, cramps, pain, paresthesias, carpopedal spasm). Ionized/free Ca2+ is 1° regulator of PTH; changes in pH alter PTH secretion, whereas changes in albumin do not.
Parathyroid hormone
Source: Chief cells of parathyroid. Function: ↑ bone resorption of Ca2+ and PO43-.↑ kidney reabsorption of Ca2+ in distal convoluted tubule.↓ reabsorption of PO43- in proximal convoluted tubule.↑ 1,25-(OH)2 D3 (calcitriol) production by stimulating kidney 1α-hydroxylase in proximal. convoluted tubule. ↑ serum Ca2+, ↓ serum PO43-, ↑ urine PO43-, ↑ urine cAMP.↑ RANK-L (receptor activator of NF-κB ligand) secreted by osteoblasts and osteocytes. Binds RANK (receptor) on osteoclasts to stimulate osteoclasts and ↑ Ca2+ → bone resorption.Intermittent PTH release can also stimulate bone formation. PTHrP functions like PTH and is commonly increased in malignancies (eg, squamous cell carcinoma of the lung, renal cell carcinoma). Regulation:↓ serum Ca2+ → ↑ PTH↑ serum PO43- → ↑ PTH↓ serum Mg2+ → ↑ PTH↓↓ serum Mg2+ → ↓ PTHCommon causes of ↓ Mg2+ include diarrhea, aminoglycosides, diuretics, alcohol abuse.
Calcitonin
Source: Parafollicular cells (C cells) of thyroid. Function: ↓ bone resorption of Ca2+.Calcitonin opposes actions of PTH. Not important in normal Ca2+ homeostasis. Regulation: ↑ serum Ca2+ → calcitonin secretion.
Thyroid hormones (T3/T4)
Iodine-containing hormones that control the body's metabolic rate.T4 major form in blood (longer half-life), conversion to T3 (more potent) Source: Follicles of thyroid. 5'-deiodinase converts T4 (the major thyroid product) to T3 in peripheral tissue. T3 binds nuclear receptor with greater affinity than T4. Peripheral conversion is inhibited by glucocorticoids, β-blockers and propylthiouracil (PTU). Thyroid peroxidase is responsible for oxidation, organification of iodide and coupling of monoiodotyrosine (MIT) and diiodotyrosine (DIT). Propylthiouracil inhibits both thyroid peroxidase and 5'-deiodinase. Methamizole inhibits thyroid peroxidase only. Function: - Bone growth (synergism with GH)- Brain maturation- β-adrenergic effects. ↑ β1 receptors in heart → ↑ CO, HR, SV, contractility- Basal metabolic rate via ↑ Na+/K+-ATPase activity → ↑ O2 consumption, RR, body temperature- Blood sugar (↑ glycogenolysis, gluconeogenesis)- Break down lipids (↑ lipolysis)- ↑ cholesterol clearance Thyroxine-binding-globulin (TBG) binds most T3/T4 in blood. Bound T3/T4 = inactive. ↑ TBG in pregnancy or OCP use (estrogen → ↑ TBG) → ↑ total T3/T4↓ TBG in hepatic failure, steroids, nephrotic syndrome
Signaling pathway - Steroid hormones
Steroid hormones are lipophilic and therefore must circulate bound to specific binding globulins, which ↑ their solubility. In men, ↑ sex hormone-binding globulin (SHBG) lowers free testosterone → gynecomastia.In women, ↓ SHBG increases free testosterone → hirsutism. OCPs, pregnancy → ↑ SHBG
Cushing syndrome
Etiology: ↑ cortisol due to:- Exogenous corticosteroids: result in ↓ ACTH, bilateral adrenal atrophy. Most common cause.- Primary adrenal adenoma, hyperplasia, or carcinoma – result in ↓ ACTH, atrophy of uninvolved adrenal gland.- ACTH-secreting pituitary adenoma (Cushing disease); paraneoplastic ACTH secretion (eg, small cell lung cancer, bronchial carcinoids) – result in ↑ ACTH, bilateral adrenal hyperplasia.Cushing disease is responsible for the majority of endogenous cases of Cushing syndrome. Findings: Hypertension, weight gain, moon facies, abdominal striae and truncal obesity, buffalo hump, skin changes (eg, thinning, striae), hirsutism, osteoporosis, hyperglycemia (insulin resistance), amenorrhea, immunosuppression. Can also present with pseudohyperaldosteronism. Diagnosis: - Screening tests: ↑ free cortisol on 24-hr urinalysis, ↑ midnight salivary cortisol, and no suppression with overnight low-dose dexamethasone test. - Measure serum ACTH:→ If ↓, suspect adrenal tumor or exogenous glucocorticoids. → If ↑, distinguish between Cushing disease and ectopic ACTH secretion with a high-dose (8 mg) dexamethasone suppression test. - Ectopic secretion will not decrease with dexamethasone because the source is resistant to negative feedback. - Ectopic secretion will not increase with CRH because pituitary ACTH is suppressed.
Adrenal insufficiency
Inability of adrenal glands to generate enough glucocorticoids +/- mineralocorticoids for the body's needs. Symptoms include weakness, fatigue, orthostatic hypotension, muscle aches, weight loss, GI disturbances, sugar and/or salt craving. Diagnosis:- Measurement of serum electrolytes, morning/random serum cortisol and ACTH→ low cortisol, high ACTH in 1° adrenal insufficiency→ low cortisol, low ACTH in 2°/3° adrenal insufficiency due to pituitary/hypothalamic disease, and response to ACTH stimulation test- Alternatively, can use metyrapone stimulation test: metyrapone blocks last step of cortisol synthesis (11-deoxycortisol → cortisol). Normal response is ↓ cortisol and compensatory ↑ ACTH and 11-deoxycortisol. → In 1° adrenal insufficiency, ACTH is ↑ but 11-deoxycortisol remains ↓ after test. → In 2°/3° adrenal insufficiency, both ACTH and 11-deoxycortisol remain ↓ after test.
Primary adrenal insufficiency
Deficiency of aldosterone and cortisol production due to loss of gland function → hypotension (hyponatremic volume contraction), hyperkalemia, metabolic acidosis, skin and mucosal hyperpigmentation (due to ↑ MSH, a byproduct of ACTH production from proopiomelanocortin [POMC]). - Acute – sudden onset (eg, due to massive hemorrhage). May present with shock in acute adrenal crisis.- Chronic – Addison disease. Due to adrenal atrophy or destruction by disease (autoimmune destruction most common in the Western world; TB most common in the developing world). - Associated with autoimmune polyglandular syndromes. - Waterhouse-Friderichsen syndrome – acute 1° adrenal insufficiency due to adrenal hemorrhage associated with septicemia (usually Neisseria meningitidis), DIC, endotoxic shock.
Secondary adrenal insufficiency
Seen with ↓ pituitary ACTH production. No skin/mucosal hyperpigmentation, no hyperkalemia (aldosterone synthesis preserved due to intact renin-angiotensin-aldosterone axis).
Tertiary adrenal insufficiency
Seen in patients with chronic exogenous steroid use, precipitated by abrupt withdrawal. Aldosterone synthesis unaffected.
Hyperaldosteronism
Increased secretion of aldosterone from adrenal gland. Clinical features: hypertension, fatigue, muscle weakness, paresthesias, headaches, ↓ or normal K+, metabolic alkalosis. 1° hyperaldosteronism does not directly cause edema due to aldosterone escape mechanism. However, certain 2° causes of hyperaldosteronism (eg, heart failure) impair the aldosterone escape mechanism, leading to worsening edema. Primary hyperaldosteronism: Seen with adrenal adenoma (Conn syndrome) or bilateral adrenal hyperplasia. ↑ aldoserone, ↓ renin. Causes resistant hypertension. Secondary hyperaldosteronism: Primary over-secretion of renin secondary to a decrease in renal blood flow. Seen in patients with renovascular hypertension, juxtaglomerular cell tumor (renin-producing). Sequestration of blood on the venous side of the systemic circulation, edema (eg, cirrhosis, heart failure, nephrotic syndrome). ↑ aldosterone, ↑ renin.
Neuroendocrine tumors
Heterogeneous group of neoplams originating from Kulchitsky and enterochromaffin-like cells. Most tumors arise in the GI system (eg, carcinoid, gastrinoma), pancreas (eg, insulinoma, glucagonoma), and lungs (small cell carcinoma). Other organs include thyroid (eg, medullary carcinoma), and adrenals (eg, pheochromocytoma). Cells contain amine precursor uptake decarboxylase (APUD) and secrete different hormones (eg, 5-hydroxyindoleacetic acid [5-HIAA], neuron-specific enolase [NSE], chromogranin A).
Neuroblastoma
Most common tumor of the adrenal medulla in children, usually <4 years old. Originates from neural crest cells. Occurs anywhere along the sympathetic chain. Most common presentation:- Abdominal distension - Firm, irregular mass that can cross the midline (vs Wilms tumor, which is smooth and unilateral)- Less likely to develop hypertension than with pheochromocytoma- Can present with opsoclonus-myoclonus syndrome ("dancing eyes-dancing feet") - ↑ homovallinic acid (HVA) and vanillylmandelic acid (VMA) in urine (catecholamine metabolites).- Homer-Wright rosettes characteristic of neuroblastoma and medulloblastoma- Bombesin and NSE ⊕- Associated with overexpression of N-myc oncogene- Classified as an APUD tumor
Pheochromocytoma
Most comon tumor of the adrenal medulla in adults. Derived from chromaffin cells (arise from neural crest).Up to 25% of cases associated with germline mutations (eg, NF-1, VHL, RET [MEN 2A, 2B]). Symptoms: - Most tumors secrete epinephrine, norepinephrine, and dopamine, which can cause episodic hypertension, headaches, perspiration, palpitations, pallor- Symptoms occur in "spells" – relapse and remit- May also secrete EPO → polycythemia Findings: ↑ catecholamines and metanephrines in urine and plasma Treatment: Irreversible α-agonists (eg, phenoxybenzamine) followed by β-blockers prior to tumor resection. Rule of 10's:10% malignant10% bilateral10% extra-adrenal (eg, bladder wall, organ of Zuckerkandl)10% calcify10% kids
Hashimoto thyroiditis
Most common cause of hypothyroidism in iodine-sufficienct regions.An autoimmune disorder with antithyroid peroxidase (antimicrosomal) and antithyroglobulin antibodies.- Associated with HLA-DR3, DR5.- ↑ risk of non-Hodgkin lymphoma (typically of B-cell origin). May be hyperthyroid early in course due to thyrotoxicosis during follicular rupture. Histologic findings: Residual follicles surrounded by Hürthle cells (large oxyphilic cells filled with granular cytoplasm), mononuclear infiltrate consisting of lymphocytes and plasma cells with germinal centers. Findings: diffusely moderately enlarged, nontender thyroid.
Congenital hypothyroidism (cretinism)
Severe fatal hypothyroidism due to antibody-mediated maternal hypothyroidism, thyroid agenesis, thyroid dysgenesis (most common cause in US), iodine deficiency, dyshormonogenetic goiter. Findings: the 6 P's- Pot-bellied- Pale- Puffy-faced- Protruding umbilicus- Protuberant tongue- Poor brain development
Subacute granulomatous thyroiditis (de Quervain)
Self-limited disease often following a flu-like illness (eg, viral infection). May be hyperthyroid early in course, followed by hypothyroidism (permanent in ~15% of cases).- Do not have increased radioactive iodine uptake, "leaks" thyroid hormone out of damaged gland. Histology: granulomatous inflammation with multinucleated giant cells, disrupted follicles Findings: ↑ ESR, jaw pain, very tender thyroid.
Riedel thyroiditis
Thyroid replaced by fibrous tissue with inflammatory infiltrate.Fibrosis may extend to local structures (eg, trachea, esophagus), mimicking anaplastic carcinoma. 1/3 are hypothyroid. Considered a manifestation of IgG4-related systemic disease (eg, autoimmune pancreatitis, retroperitoneal fibrosis, noninfectious aortitis). Findings: fixed, hard (rock-like), painless goiter. Histology: Dense fibrous tissue extending beyond the tyroid capsule.
Wolff-Chaikoff effect
Thyroid gland downregulation in response to ↑ iodide. Excess iodine temporarily inhibits thyroid peroxidase → ↓ iodine organification → T3/T4 production. Opposite of Jod-Basedow phenomenon.
Graves disease
Most common cause of hyperthyroidism.Thyroid-stimulating immunoglobulin (IgG; type II hypersensitivity) stimulates TSH receptors on thyroid (hyperthyroidism, diffuse goiter) and dermal fibroblasts (pretibial myxedema). Infiltration of retroorbital space by activated T-cells → ↑ cytokines (eg, TNF-α, IFN-γ) → ↑ fibroblast secretion of hydrophilic GAGs → ↑ osmotic muscle swelling, muscle inflammation, and adipocyte count → exophthalmos. Often presents during stress (eg, pregnancy). - Associated with HLA-DR3 and HLA-B8. Histology: Tall, crowded follicular epithelial cells projecting into the follicular lumen; scalloped colloid.
Toxic multinodular goiter
Focal patches of hyperfunctioning follicular cells distended with colloid working independently of TSH (due to TSH receptor mutations in 60% of cases). ↑ release of T3 and T4. Hot nodules are rarely malignant.
Thyroid storm
Uncommon but serious complication that occurs when hyperthyroidism is incompletely treated/untreated and then significantly worsens in the setting of acute stress such as infection, trauma, surgery. Presents with agitation, delirium, fever, diarrhea, coma, and tachyarrhythmia (cause of death). May see ↑ LFTs. Treat with the 4 P's:- β-blockers (eg, Propanolol)- Propylthiouracil- Corticosteroids (eg, Prednisolone)- Potassium iodide (Lugol iodine)
Jod-Basedow phenomenon
Thyrotoxicosis if a patient with iodine deficiency and partially autonomous thyroid tissue (eg, autonomous nodule) is made iodine replete. Can happen after iodine IV contrast. Opposite to Wolff-Chaikoff effect.
Thyroid cancer
Papillary, follicular, medullary, undifferentiated/anaplastic Typically diagnosed with fine needle aspiration; treated with thyroidectomy. Complications of sugery:- Hoarseness (due to recurrent laryngeal nerve damage)- Hypocalcemia (due to removal of parathyroid glands)- Transection of recurrent and superior laryngeal nerves (during ligation of inferior thyroid artery and superior laryngeal artery, leading to dysphagia, dysphonia) Recurrent laryngeal nerve → all intrinsic muscles of the larynx with exception of the cricothyroid musclesSuperior laryngeal nerve → cricothyroid muscle
Thyroid adenoma
Benign solitary growth of the thyroid. Most are nonfunctional ("cold"), can rarely cause hyperthyroidism via autonomous thyroid hormone production ("hot" or "toxic"). Most common histology is follicular; absence of capsular or vascular invasion (unlike follicular carcinomas).
Hypoparathyroidism
Due to acciental surgical excision of parathyroid glands, autoimmune destruction, or DiGeorge syndrome. Findings: tetany, hypocalcemia, hyperphosphatemia.- Chvostek sign – tapping of facial nerve → contraction of facial muscles- Trousseau sign – occlusion of brachial artery with BP cuff → carpal spasm Pseudohypoparathyroidism type 1A – unresponsiveness of kidney to PTH → hypocalcemia despite ↑ PTH levels. Presents as a constellation of physical findings known as Albright hereditary osteodystrophy: shortened 4th/5th digits, short stature, obesity, developmental delay. Autosomal dominant. Due to defective Gs protein α-subunit causing end-organ resistance to PTH. Defect must be inherited from mother due to imprinting.Pseudopseudohypoparathyroidism – physical exam features of Albright hereditary osteodystrophy but without end-organ PTH resistance (PTH level normal). Occurs when defective Gs protein α-subunit is inherited from father.
Pseudohypoparathyroidism type 1A
Also known as Albright hereditary osteodystrophy. Unresponsiveness of kidney to PTH → hypocalcemia despite ↑ PTH levels- Due to defective GS protein α-subunit causing end-organ resistance to PTH- Autosomal dominant- Defect must be inherited from mother due to imprinting ↓ Ca2+ despite ↑ PTH levels Presentation:- Shortened 4th/5th digits- Short stature- Obesity- Developmental delay
Pseudopseudohypoparathyroidism
Physical exam features of Albright hereditay osteodystrophy (shortened 4th/5th digits, short stature) but without end-organ PTH resistance (PTH levels normal). - Occurs when defective Gs protein α-subunit is inherited from father.
