Neuroendocrine Flashcards
Hypothalamus and posterior pituitary
Hypothalamic magnocellular neurons in supraoptic nucleus and paraventricular nucleus
-Vasopression released in response to changes in osmotic pressure, controls water balance
-Oxytocin promotes uterine contraction during birth and milk ejection after birth
Hypot
Hypothalamic parvocellular neurons produce releasing and inhibitory hormones
In preoptic: (GnRH- Gonadotropin releasing hormone)
In arcuate and ventromedial (GHRH-Growth hormone releasing hormone)
In periventricular (TRH-thyrotroph releasing hormone, CRH- corticotroph releasing hormone, somatostatin)
Im paraventricular (TRH, CRH, PRF-prolactin releasing factor)
SON = Supraoptic nucleus, PVN = Paraventricular
Hypothalamus and anterior pituitary
Hypothalamic parvocellular neurons produce releasing and inhibitory hormones:
- In preoptic: GnRH- Gonadotropin releasing hormone)
- In arcuate and ventromedial: GHRH-Growth hormone releasing hormone)
- In periventricular: TRH-thyrotroph releasing hormone, CRH- corticotroph releasing hormone, somatostatin)
- In paraventricular: TRH, CRH, PRF-prolactin releasing factor
Preoptic area
Regulatory function: Parasympathetic/Temp reg/male sex behavior
Pathology: Hyperthermia/men: low libido/parenting
Medial/preoptic
Regulatory function: Thirst/Drinking
Pathology: Polydipsia/Adipsia
Suprachiasmatic
Regulatory function: Circadian rhythm
Pathology: Sleep/wake disturbance
Anterior
Regulatory function: Cooling/Parasympath.
Pathology: Hyperthermia (B/L)
Dorsomedial
Regulatory function: ANS/Aggression/Satiety
Pathology: Hyperphagia
Ventromedial
Regulatory function: Satiety/ sex behavior
Pathology: Hyperphagia (B/L)
Posterior
Regulatory: Heating/Sympathetic
Pathology: Poikilothermia (B/L)
Lateral
Regulation: Hunger
Pathology: Aphagia
Sellar masses - etiology
Benign tumors:
- Pituitary adenoma (most common sellar mass in
adults, from 3rd decade on)
- Craniopharyngioma
- Meningioma
Malignant tumors (primary or metastases)
- Cysts
- Infections (rare - abscess, tuberculoma)
- Lymphocytic Hypophysitis
- Carotid Aneurysm
Hypothalmic damage
Severe memory loss, obesity, and personality changes (apathy, aggressive antisocial behavior, severe food cravings, inability to work or attend school, poor concentration)
2/2 extrasellar extension of pituitary tumors, hypothalamic radiation, or damage from surgical removal of parasellar tumors
Sellar masses clinical presentation
Neurologically: Visual loss, headache, diplopia, CSF rhinorrhea, pituitary apoplexy
Hormonally: Excessive hormone secretion (a pituitary adenoma, stalk compression), hypopituitarism (any sellar mass)
Incidentally, on a radiologic procedure
Pituitary apoplexy
Sudden hemorrhage into a pituitary adenoma
Acute, severe headache, impaired vision, meningeal irritation, nausea
Acute deficiency of pituitary hormones (most importantly of ACTH)
MRI: radiologic study of choice
Treatment: medical (glucocorticoid) ± surgical (early) if there are visual changes
Pituitary Adenomas
Benign, true neoplasms
Micro or macroadenomas (< 1 cm or > 1 cm)
Classification by cell type:
• Lactotroph -High prolactin, hypogonadism
• Corticotroph - Cushing’s syndrome
• Somatotroph - Acromegaly
• Gonadotroph - clinically nonfunctioning, OHS (ovarian hyperstimulation), premature puberty
• Thyrotroph - clinically nonfunctioning, hyperthyroidism
Lactotroph adenomas
40% of all pituitary adenomas
Majority are microadenomas, rarely grow
Clinical manifestations: Hyperprolactinemia: galactorrhea (women), impotence (men), hypogonadism (women and men)
Diagnosis: High prolactin parallels tumor size
Dopamine agonists- Act on D2 receptors on the lactotroph cell
- Goal: Normalization of PRL/ decrease tumor size
- Two approved for treatment of high PRL / lactotroph adenomas: Bromocriptine (Parlodel®) 1.25-2.5mg/d, Cabergoline(Dostinex®) 0.25 mg p.o. biw w/dinner
- Side effects: mostly GI (nausea, constipation), headache, postural hypotension, depression
- Decrease in prolactin occurs within 2-3 weeks after treatment begins, usually precedes a decrease in size of tumor
Corticotroph Adenomas
Clinical: Cushing’s syndrome
Diagnosis: Elevated 24 hour urine free cortisol and a high-normal or high ACTH
Treatment: Transsphenoidal surgery (80% cure rate) ± pituitary irradiation (45-85% cured) ± total B/L adrenalectomy
Somatotroph adenomas
Clinical syndrome: Acromegaly (in adults), gigantism (in children)
Diagnosis: Elevated IGF-1, high GH after an oral glucose load (OGTT)
Treatment: Transsphenoidal surgery (60% cure rate) ± medical treatment (dopamine agonists, somatostatin analogues, GH receptor antagonist) ± XRT
Physiologic Enlargement of the Pituitary
Lactotroph Hyperplasia (most frequent)-during pregnancy
Thyrotroph Hyperplasia- due to long-standing untreated primary hypothyroidism
Gonadotroph Hyperplasia-due to long-standing untreated primary hypogonadism
Somatotroph and Corticotroph Hyperplasia -due to neuroendocrine tumors and gangliocytomas
Treatment: Treat the cause of the hyperplasia, e.g. treat the primary hypothyroidism or hypogonadism, clearly nothing has to be done to the pituitary itself
Craniopharyngiomas
Benign tumors, solid or solid-cystic
Arise from remnants of Rathke’s pouch
Peak of incidence: 11-20 and 41-50 yrs
Clinically: Growth retardation (children), increased ICP, hypopituitarism and DI
Radiologically: Calcifications on CT (not pathognomonic)
Treatment: If symptomatic, surgical resection (if possible) followed by XRT for residual tumor
Lymphocytic hypophysitis
Post-partum (most frequent), women not post-partum and men; autoimmune?
Clinically: Headache out of proportion to sellar mass, hypopituitarism (prominent ACTH deficiency), DI
MRI: enlarged pituitary, delayed or absent enhancement of the posterior pituitary
Rx: partial recovery is possible
SIADH
Hypotonic hypoNa+, impaired urinary dilution
Congenital or acquired: trauma, stroke, drugs, infections, AML, Guillain-Barré, MS, hydrocephalus, delirium tremens, psychosis, cerebrovascular occlusion/hemorrhage, cavernous sinus thrombosis,
Treatment: cause, water restriction
Central DI
Polyuria (>3L), usually nocturia, dilute urine
Destruction of >80% magnocellular neurons, congenital or acquired: tumors, granulomas, AI, vascular, idiopathic, trauma
Treatment: DDAVP (nasal spray, oral, injectable)
Adipsic hypernatremia
Hypertonic dehydration, lack of thirst
Selective defect in hypothalamic osmoreceptors, congenital or acquired: ACOM aneurysms, tumors, granulomas, psychologic
Treatment: Water intake based on weight
AEDs and endocrine issues
PCOS (more frequent with valproate) / Infertility/Anovulatory cycles
Low bone mineral density
Bipolar disorders and some antipsychotics
Wt gain (Lithium, valproate), menstrual abnls., Li - hypothyroidism
Atypical antipsychotics;
Wt gain, fasting hyperinsulinemia, diabetes mellitus, and DKA
Na abnormalities/Medical situation/Symptoms
HypoNa/1. SIADH, adr insuff 2. diarrhea, diuretic, poor PO 3. CHF, cirrhosis/Lethargy, confusion, seizures, coma; osmotic demyelination if too rapid correction
HyperNa/DI, dehydration/Lethargy, confusion
Hypokalemia/Medical situation/Symptoms
Hypokalemia/Vomiting, diuretic, diarrhea, RTA/Myopathy, profound weakness
Ca, Mg abnormalities/Medical situation/Symptoms
Hypercalcemia/Inc PTH, malignancy, bone mets/Obtundation
Hypocalcemia, hypomagnesemia/Parathyroidectomy - Ca, Cisplatin - Mg/Increased DTRs, tetany, seizures
Hypermanganese
2/2 TPN, cholestatic liver disease, resulting in Parkinsonism, with MRI hyper intensities in base ganglia
Osmotic demyelination
-Previously referred to as central pontine myelinolysis but there is extrapontine myelinolysis
-Occurs following rapid correction of hyponatremia
-Clinical: dysarthria, dysphagia, abducens palsies, coma, flaccid quadriplegia
Neuropsychiatric lupus
Neurosarcoidosis epidemiology
15% of patients with sarcoidosis may have neurological complicsyiond f
Half of neurosarcoidosis cases are diagnosed before autopsy (1993)
More than half of patients with systemic sarcoidosis who develop neurologic symptoms do so within 2 years of systemic diagnosis (1995)
Protean manifestations affecting any part of nervous system
Neurosarcoidosis presentation
Neurosarcoidosis in imaging
Leptomeningeal vs pachymeningeal
Lepto- involves pia mater and arachnoid mater
Pachy- involves dura and arachnoid mater
Renal disease: neurological problems with dialysis/CKD
Headache (Triptans) 60% patients (r/o subdurals!)
Polyneuropathy (end stage creatinine clearance<5 ml/min)
cramps, restless legs improves with transplantation > dialysis
AV shunt “steal” neuropathy: carpal tunnel due to amyloid deposition after several years of dialysis, beta-2-microglobulin not well dialyzed
Dysequilibrium - H/A, vomitting, increased ICP; idiogenic osmoles create gradient shifting water into brain
Chronic uremia - cognitive symptoms very common
Seizures: beware heavily protein bound AEDs free level
Nephrogenic systemic fibrosis
Nephrogenic systemic fibrosis
Neurologic complications of celiac disease