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Endocrine: Pituitary

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Three functions of Prolactin
Breast development; Milk production; Sexual gratification
LH functions
Females: Triggers ovulation, Devt of corpus luteum;
Males: Production of testosterone by Leydig cells
FSH functions
Females: Follicle growth and oogenesis;
Males: Spermatogenesis
ACTH function
Stimulates Adrenal cortex to release the cortical triad: Aldosterone, Cortisol, Androgens
GH (STH) function
Stimulates growth, mitosis, and protein synthesis at bones and muscles
IGF-1 site of origin and function
Made at liver; mediates [and is agonist for] GH effects
Four Oxytocin functions
Cervical dilation, Uterine contractions, Milk let-down, Neurotransmitter
ADH alternate name and function
Vasopressin; Anti-diuresis [H2O reabsorption] and vascular constriction
Pituitary masses epidemiology
Most are benign, but many secrete 1 or more hormones; 10% of all reported intracranial masses; ≤25% pop
Microadenoma vs macroadenoma
≤1cm X ≥1cm
Most common pituitary adenomas; effect and gender distribution. Which MEN do they appear in?
Prolactinomas; hyperprolactinemia; gynecomastia; mostly female. Appear in MEN1 [pituitary, parathyroid, pancreas].
Symptoms of Hyperprolactinemia
Galactorrhea, Breast enlargement & tenderness, Anovulatory amenorrhea, dysmenorrhea, decreased libido, ED
Hyperprolactinemia treatment
Bromocriptine [Parlodel- a DA agonist] or Cabergoline [Dostinex- an ergot derivative used to Tx Parkinson's, associated with gambling compulsion]
Bromcriptine uses; Mechanism; Contraindications
-Dopamine agonist used in the treatment of pituitary tumors, Parkinson's, Hyperprolactinaemia, Neuroleptic Malignant Syndrome, and DM2.
-For Hyperprolactinemia, given as Parlodel;
-Avoid in Breastfeeding, because decreases Prolactin;
Bromcriptine interactions
-Triptans [serotonin receptor agonists in migraine treatment],
-Decongestants [HTN/tachy],
-Antipsychotics [hTN]
Cabergoline use; Trade; Mechanism; Contraindications
-Hyperprolactinemia treatment [Dostinex];
-DA agonist @ anterior pituitary,
-Decreases Prolactin
-Contraindicated in Breastfeeding
Short Stature diagnostic criteria
2 SDs below average for age/gender;
Gold Standard: Insulin tolerance [0.1ug/kg] followed by sampling for GH. If GH <5 [10 in kids] POS for GH deficiency
Short stature treatment. What interactions and side-effects exist?
GH daily injection: Nutropin, Humatrope, Genotropin; Increase [glu], decrease INR in Coumadin pts; Diabetes, HTN, Pancreatitis
Acromegaly diagnosis and treatment. What side effects are there?
GH levels 1 hr after 1 hr-GTT are >1µ/L;
Surgical resection & Octreotide IM (Sandostatin) or Lanreotide IM (Somatuline);
Cardiomegaly/CHF, HTN, Diabetes, RF, HA, visual disturbance from tumor
Thyroxine forms & distribution
T4: 90%, T3: 10% (4X [T4]); 99% is bound to TBG [Thyroid Binding Globulin]. Only free hormone is active.
Element required for thyroxine
Iodine
Cells producing T4 & mechanism
Follicular cells; bind I to Thyroglobulin [TG]
Iodine-capturing enzyme
Thyroid Peroxidase [TPO]
Thyroxine regulating gland & hormone; regulatory mechanism
TSH [Thyrotropin] made at anterior pituitary in response to T4 levels
Second Thyroid hormone and function
Calcitonin, Ca2+ regulator. Opposes PTH-- decreases serum [Ca2+]
Hypothyroid S/s
Fatigue, Wt gain, Depression, Hair loss, Dry skin, Dysmenorrhea, Brady
Hypo-Iodine incidence
9% omnivores, 25% vegetarians, 80% vegans are LOW
Hashimoto's; Gender distribution; Mechanism
Autoimmune hypothyroidism; 10X more female; Thyroid Peroxidase ABs bind & inhibit T4; Insidious onset w/ hyPER-thyroid 1st; Hi Genetics
Hashimoto's Labs
TPO-antibody & TSH elevated; T3 and T4 depressed
Myxedema signs and symptoms
Non-pitting edema with severe hypothyroidism,
Reduced CO, Mental slowing. May result in myxedemic coma precipitated by stroke/MI
Hypothyroidism treatment & allergic issue; alternative
Levothyroxine [Synthroid or Levothroid]; Made with lactose binder OR
Dessicated thyroid (porcine or bovine)
Thyroid replacement monitoring
Monitor TSH, also T3/T4;
NB: T3 replacement suppresses TSH
Grave's disease hallmarks
Autoimmune Hyperthyroidism [Agonist effect]; Nervous, Tachy, Weight loss, Exophthalmia, Hyperhidrosis, Tremor, Insomnia
Grave's drugs names, mechanism; side effects
Methimazole and Propylthiouracil; Inhibit addition of iodine to Thyroglobulin to block T4 synthesis; Leukopenia, Agranulocytosis, Aplastic Anemia; Hepatotoxicity (PTU also alters INR in Coumadin Tx
1st line Grave's treatment
Methimazole (Tapazole), Propylthiouracil (PTU)
2nd line Grave's treatment
Ablation (w/ I-131) or thyroidectomy, followed by thyroid replacement Tx
Acute thyroiditis eponym, diagnosis, & treatment
-De Quervain's [also toxic thyroiditis]
-Hyperthyroidism secondary to infection. Differentiate from Grave's by:
1. recent URI or viral infection
2. elevated CRP and ESR
3. radioactive I uptake. [I-131 uptake by Grave's is high, uptake by acute thyroiditis is low;
-Treatment for acute is oral steroids
Thyroid mass epidemiology and evaluation
-40-50% adults;
-Usually benign tumors but may be cysts [rare]; --Ultrasound is Gold Standard, Cysts usually resolve, but may needle aspirate
Thyroid nodule treatment
-Ignore unless >1.5 cm, then do US and/or aspirate
-If unsure, do I-131 uptake. Active uptake ["hot"] is OK. No uptake ["cold"] may be malignant -> biopsy
Four kinds of thyroid tumors
1. Papillary [75%, most female, rarely metastasize, treatment: resection];
2. Follicular [15%, women > 50 yrs, may metastasize to lung/bone, treatment: resection or I-131];
3. Medullary [5%, very aggressive, metastatic to liver, lung, bone; treatment: resection];
4. Anaplastic carcinomas [5%, very aggressive with poor prognosis, treatment: radiation/chemo]
Post-thyroidectomy treatment
The sequence is:
1. Whole-body I-131 scan to destroy any metastases;
2. High-dose RAI ablation; repeat in 1 year;
3. High-dose Levo-T4 for 5 yrs to ensure TSH is not present, [unidentified metastasis], then normal dose
Thyroid replacement drug that replaces endogenous T3
Liothyronine [Cytomel]; used in conjunction with Levothyroxine for patients with poor T4-> T3 conversion.
When thyroidectomy is done
When there is significant obstructive thyromegaly.
Otherwise, radio-iodine ablation is used.
Treatment for acute thyroiditis
Corticosteroids to reduce inflammation
Distinguishing cancerous thyroid nodules from benign
I-132 uptake scan:
"Hot" [I-131 uptake POS] are usually benign,
"Cold" [I-132 uptake NEG] are likely malignant-- biopsy!!
Only definitive thyroid cancer diagnostic procedure.
Biopsy [needle or tissue]
Relationship between thyroid CA & labs
None: Thyroid CA is not associated with T3/T4/TSH changes.
Adrenal cortex regions and hormones
Go Find Rex, Make Good Sex;
Granulosa [Mineralocorticoid-> aldosterone];
Folliculata [Glucocorticoid-> cortisol];
Reticularis [DHEA-> -> testosterone]
1st line Adrenal Insufficiency treatment and side effects
Adrenal insufficiency-> Addison's-> ADD cortisol!
-Hydrocortisone = Cortef 25-30 qDay, divided BID;
-Side effects: Weight gain, HTN, Immuosuppression, DM
Two hormones with mild mineralocorticoid activity
Progesterone & Deoxycorticosterone
Cortisol effects
Increase BP, Increase glucose [by gluconeogenesis], inhibit insulin, antidiuretic [water retention]
Cortisol diurnal cycle
Lowest 3 hrs into sleep;
Highest in early morning
Adrenal insufficiency name and hallmarks
-Addison's;
-Fatigue, dizzy, weakness, weight loss, diarrhea, hypotension, hyperpigmentation
Adrenal Insufficiency Types
-Primary: Adrenal dysfunction;
-Secondary: Ant pituitary fails to make ACTH;
-Tertiary: Hypothalamus fails to make CRH;
-Autoimmune: secondary to DM-1, Grave's, or Hashimoto's
Addisonian Crisis occurence, & signs and symptoms
-In untreated Addison patient or Addison patient with Infection or sepsis [often meningococcal septicemia = Wterhouse Friderichson];
-Fever, hypotension, vomiting, diarrhea, dehydration, weakness, , hypoglycemia,
2nd line adrenal insufficiency treatment
Prednisone or prednisolone. Has less mineralocorticoid activity then hydrocortisone
Mineralocorticoid replacement drug
Fludrocortisone [usually used with hydrocortisone in Addison's]
Adrenal excess condition
Cushing's
Ranked causes of Cushing's
1. Iatrogenic (corticosteroids/steroids);
2. Secondary (pituitary mass/tumor);
3. Primary (adrenal adenoma);
4. Ectopic tumor (Small cell lung CA producing ACTH)
Cushing's initial diagnostic lab test
Elevated cortisol in serum & 24-hr urine
Cushing's diagnostic details
Dexamethasone suppression test is NEG:
1. If ACTH: Absent/Low; Cortisol: Not suppressed by high Or low doses; Diagnosis is: Primary
2. If ACTH: Elevated; Cortisol: not suppressed by low, but is suppressed by high; Diagnosis is Secondary
3. If ACTH: Normal to Elevated; Cortiusol: Not suppressed by high OR low doses; Diagnosis: MEN
Cushing's signs and symptoms
Central obesity, Moon face, buffalo hump, hirsutism, amenorrhea, truncal striae, HTN, acne
Cushing's treatment
Iatrogenic: discontinue meds;
Secondary: Resection of pituitary tumor
Primary: Resection of adrenal adenoma
Follow resections by hormone replacement until ACTH rises again
Neuroendocrine adenomas that release catecholamines
Phaeochromocytoma
Phaeo signs and symptoms
HTN, tachy, red flushing, palpitations, diaphoresis, anxiety, HA
Phaeo diagnosis
Plasma free metanephrine (Epi metabolite) elevated [Gold standard], 24-hr urine metanephrines/catecholamines; MRI to localize
-May be MEN2A: parathyroid, pharochromocytoma, medullary thyroid tumor
Phaeo Tx
Resection following PHENOBENZAMINE (prevents severe HTN in surgery)
Phaeo contraindicated Rx
Beta Blockers (don't block alpha sites, get rebound HTN)
Diabetes Insipidus types & etiology; Tx
1. ADH deficiency from POST pit ; Tx: vasopressin replacement (Desmopressin) given as nasal spray, OR
2. Inability to bind ADH at collecting ducts; Tx: Hydrochlorothiazide
Calcium regulating glands; MOA
Parathyroids; Resorb Ca2+ from bone, Retain Ca2+ at gut (via Vit D) and recover Ca2+ at kidney
Hypoparathyroidism S/s
Hypocalcemia-> Muscle cramps/tetany, Parasthesia, Dry hair/skin, QT elongation, Brittle nails, Seizure
Hypoparathyroidism Tx
Ca2+ & Vit D replacement, monitor regularly to avoid arrhythmia (short QT) and Stones, Bones, Moan, Groans
Hyperparathyroidism S/s
Hypercalcemia-> Stones, Bones, Moans, Groans, Thrones
Parathyroid Tumor test
Sestamibi PT scan using Tc-99m isotope (uptake is faster in hyperthyroidism)
PT tumor resection indications
Under 65, cut it out. Under: monitor
Can't find ectopic tumor but have elevated Ca? Take out largest PT gland.
How are the various types of Adrenal Insufficiency diagnosed?
ACTH Stimulation test: "Cosyntropin" is given, then cortisol levels checked.
If no (or v. slight) cortisol increase: PRIMARY Addison's;
If 2-10X increase: SECONDARY
**For AI Adrenal Insufficiency, 90% in US, measurement of 21-hydroxylase autoantibodies is done