Path 1 - Endocrine 1

drraythe's version from 2016-03-04 22:20

Endocrinology 6.1: General

Crap from the beginning of his outline

Question Answer
Explain what's happening in 1⁰ hyperfxn. 3 examples?Autonomous hypersecretion due to tumor or hyperplasia of the gland:
Explain what's happening in 2⁰ hyperfxnLesion in one organ (e.g., pituitary gland adenoma) → Secretes excess trophic hormone → long-term stimulation & hypersecretion by the target organ (e.g., adrenocortical hyperplasia w/ excess cortisol)
Explain 5 situations which can cz hyperactivity2⁰ to dzs of other organs
2⁰ to hormonal imbalances induced by xenobiotics
Hypersecretion of hormones or hormone-like factors by non-endocrine neoplasms (paraneoplastic syndromes)
Dysfxn resulting from abnormal degradation of hormone
Iatrogenic syndromes of hormone excess
Explain 4 situations which can cz hypoactivity1⁰ hypofxn
2⁰ hypofxn
Endocrine dysfxn due to failure of target cell response
Dysfxn due to failure of fetal endocrine system
**Hyperthyroidism is czd by what general kind of problem? 3 situations which fall under this cz?1⁰ hyperfxn!! It happens w/ Thyroid Carcinoma in dogs & Thyroid Adenoma/ multinodular hyperplasia in CATS
1⁰ hyperparathyroidism is czd by what general kind of problem? Two situations which fall under this cz?1⁰ hyperfxn!! Czd by fxnal adenomas & carcinomas of parathyroid glands.
The fxnal disturbances of 1⁰ hyperparathyroidism are the result of what?Persistent hypercalcemia (anorexia, vomiting, constipation, polyuria, polydipsia, generalized muscular weakness due to ↓ neuromuscular excitability)
Soft-tissue mineralization
↑ urinary calcium & phosphorus excretion w/ the formation of calculi
(predisposition to the development of nephrocalcinosis & urolithiasis)
Weakening of bones by excessive resorption (generalized ↓ in bone density w/ multiple fractures in advanced cases).
Hyperadrenocorticism associated w/ an ACTH-secreting pituitary neoplasm → What kind of problem? What cells are the actual dysfxning ones? What does this dysfxn result in? Fxnal disturbances & lesions of this develop from?2⁰ hyperfxn Derived from corticotroph (ACTH-secreting) cells in either the pars distalis or the pars intermedia of dogs. Result in a clinical syndrome of cortisol excess (Cushing’s Dz) by czing 2⁰ hyperfxn of the adrenal cortex. Fxnal disturbances & lesions develop from the combined gluconeogenic, lipolyitc, protein catabolic & anti-inflammatory effects of the glucocorticoid hormones on many organs. (see
CS/Lesions of Cushing’s Dz [pp.16-17])
_________ is an important mechanism resulting in hypofxn of the thyroid gland, adrenal cortex, pancreatic islets, parathyroid & hypothalamusImmune-mediated injury
3 big reasons for 1⁰ hypofxnExcessive destruction of secretory cells by a dz process, Failure of an endocrine organ to develop properly (aplasia or hypoplasia), Specific biochemical defect in the synthetic pathway of a hormone
CS/lesions of CushingsDiabetes Mellitus
Obesity, osteoporosis (XS cortisol ↑ Ca excretion by the kidneys & ↓ Ca absorption from the intestines)
Hirsutism (esp. in PDH), polyuria/polydipsia (due to hyperglycemia? Effect on ADH?)
Polyphagia (due to direct effect &/or tumor effect on hypothalamus, hepatomegaly (due to steroid hepatopathy, i.e., ↑ glycogen in hepatocytes)
Pendulous abdomen (due to muscle atrophy/weakness & hepatomegaly)
Muscular asthenia & wasting are due to ↑ catabolism of proteins + ↓ protein synthesis in skeletal myocytes
Skin lesions (90% of cases): Dermal atrophy, Bilateral symmetric alopecia, etc.
Dystrophic mineralization of skin (“calcinosis cutis”) & lung, active skeletal muscle, stomach (due to altered collagen/elastin)
↑ susceptibility to bacterial infections of skin
Urinary tract, etc. (due to anti-inflammatory effects)
Lymphopenia/lymphoid involution
CS/Lesions of HypothyroidismReduction in basal metabolic rate manifested as:
Weight gain
Muscular weakness & slow reflexes
Skin lesions (hyperkeratosis ↑ scaliness (seborrhea), bilateral symmetric alopecia (telogen hairs), Follicular keratosis, Hyperpigmentation due to ↑ number of melanocytes in the basal layer, Myxedema (accumulation of mucin = glycosaminoglycans + protein) )
Reproductive abnormalities (lack of libido, infertility (reduction in sperm count due to atrophy of spermatogenic epithelium in the testes, abnormal or absent estrus cycles, reduced conception rates) )
Joint pain & effusion
↓ plasma bound iodine (PBI)
↓ T4 & T3
Normocytic Normochromic Anemia
↑ serum cholesterol (Hypercholesterolemia (due to ↓ rate of lipid metabolism w/ ↓ intestinal excretion of cholesterol & conversion of lipids into bile acids) can result in atherosclerosis (coronary & cerebral vessels)
Glomerular & Corneal lipidosis
Pituitary aplasia & dwarfism → Common in who? What is this condition due to (embryo)GSD, Spitz, toy Pinscher & Carelian bear dogs is due to failure of the oropharyngeal ectoderm of Rathke's pouch to differentiate into trophic hormone-secreting cells of the pars distalis
Juvenile panhypopituitarism is inherited as an autosomal recessive trait in who?GSD (GSD pic where that pup was born without ability to pituitary)
Pituitary aplasia & dwarfism → What are the lesions?Pituitary Aplasia: Progressively enlarging Multiloculated cyst in the sella turcica, absence of the adenohypophysis.
Pituitary Dwarfism: Slower growth, Stunting, Bilaterally symmetric alopecia & Progressive hyperpigmentation of the skin
Congenital dyshormonogenetic goiter → What kind of dysfxn is this? Who does this happen in?(1⁰ hypofxn) autosomal recessive disorder in some breeds of sheep (Corriedale, Dorset Horn, Merino & Romney breeds), Afrikander cattle & Saanen dwarf goats; rare in dogs & cats
Congenital dyshormonogenetic goiter → What is this the result of & what are the lesions like?Result of genetic impairment of thyroglobulin synthesis; T4 & T3 levels are ↓ even though iodine uptake & turnover are ↑. Affected animals have subnormal growth rate, sparse hair coat, myxedema, weakness & sluggish behavior (most die shortly after birth). Thyroid lobes are symmetrically enlarged at birth bc of an intense diffuse hyperplasia of follicular cells
What are 3 examples of how a 2⁰ hypofxn might occur?(1) A destructive lesion in 1 organ (i.e., pituitary gland) interferes w/ the secretion of trophic hormones & results in subnormal fxn of target endocrine glands.
(2) Large, endocrinologically inactive neoplasms may interfere w/ the secretion of multiple pituitary trophic hormones & result in clinically significant hypofxn of the adrenal cortex, follicular cells of the thyroid & gonads
(3) Hypofucntion may also be 2⁰ to a lack of raw material (e.g., iodine) necessary for the synthesis of hormone (T4, T3).
Adult-onset panhypopituitarism → Non fxnal pituitary tumors. How does this cz2⁰ hypofxn? What does this result in & what does the history look like?Significant fxnal disturbances by virtue of compression atrophy of the pars nervosa & pars distalis or extension into the overlying brain & optic nerves. The clinical disturbances are related to dysfxn of the central nervous & neurohypohyseal systems as well as a lack of secretion of pituitary trophic hormones w/ diminished end-organ fxn (e.g., thyroid follicular cells, adrenal cortex & gonads). The history often includes depression, incoordination & other disturbances of balance, weakness, collapse w/ exercise, a marked change in personality & the excretion of large volumes of dilute urine w/ a ↓ specific gravity & a corresponding ↑ in water intake (PUPD)
What is an example of hypofxn due to Lack of essential raw material for hormone synthesis?Iodine-deficient goiter
Endocrine hyperactivity 2⁰ to other conditions → 3 Examples?Nutritional hyperparathyroidism
Renal hyperparathyroidism
Hormonal imbalances induced by xenobiotic chemicals
Nutritional hyperparathyroidism → Explain what is going onThere is disturbance in mineral homeostasis induced by diets with:
(1) ↓ Ca content
(2) Excess oxalate or P content w/ normal or ↓ Ca content
(3) Inadequate vitamin D3...... the resulting hypocalcemia stimulates secretion of PTH w/ subsequent chief cell hypertrophy & hyperplasia
Renal hyperparathyroidism → Explain what is going onA response to hypocalcemia resulting from chronic renal failure → progressive hyperphosphatemia (which lowers blood Ca levels) due to ↓ glomerular filtration rate (GFR) & impaired activation of vitamin D3 (effect on intestine/kidney & possible ↓ renal degradation/excretion of PTH resulting in diminished intestinal Ca transport & thus ↑ mobilization of Ca from bone)
What are the lesions associated w/ hypocalcemia due to 2⁰ renal or nutritional hyperparathyroidism?Hypertrophy & hyperplasia of chief cells, resulting in bilateral enlargement of parathyroids & excess PTH czs excessive bone resorption & marked proliferation of fibroblasts & unmineralized osteoid throughout the body (hence the term generalized fibrous osteodystrophy: bones of the skull become swollen but are soft & pliable (“big head” in horses & “rubber jaws” in dogs & cats)
Endocrine hyperactivity 2⁰ to other conditions → Hormonal imbalances induced by xenobiotic chemicals → what is an example of this?In rodents undergoing chronic toxicity testing, pituitary hyperactivity can occur → XS production of LH (due to disruption of negative feedback control by estrogen or testosterone) → ↑ incidence of tubulostromal adenomas & granulosa cell neoplasms in the ovaries of mice & of Leydig cell adenomas of the testes in rats
Hypersecretion of hormones by nonendocrine tumors → Explain this a littleCertain neoplasms of nonendocrine tissues secrete either hormones or humoral substances that share chemical &/or biologic characteristics w/ the “native” hormones secreted by an endocrine gland.
Humoral hypercalcemia of malignancy (HHM) (BE SURE TO EXPLAIN the role of PTH-rP)[PTH-rP] is parathyroid hormone-related peptide. It is NOT PTH, but it behaves similarly to PTH. So in the case of Pseudohyperparathyroidsim, autonomous hypersecretion of PTH-rP by cancer cells → PTH-rP mimics the action of PTH → inc mobilization of calcium from bone by osteoclasts → persistent life-threatening hypercalcemia
3 Situations where there is Pseudohyperparathyroidsim(Pseudohyper= Hypercalcemia occurring in association w/ a malignant neoplasm but without skeletal metastases or 1⁰ hyperparathyroidism, possibly czd by the formation of parathyroid hormone by nonparathyroid tumor tissue.)
(1) Humoral hypercalcemia of malignancy (HHM)
(2) Hypercalcemia induced by metastasis of solid neoplasms to bone
(3) Malignancies (such as Adenocarcinoma of the apocrine glands of the anal sac – dog, cat, Lymphosarcoma – dog, cat, or multiple myeloma)
What are two reasons that there would be a failure of target cells to respond to hormone?(1) A lack of adenylate cyclase in the cell membrane
(2) An alteration in hormone receptors on the cell surface
What is an example of a dz where a failure of target cells to respond to hormone is due to a lack of adenylate cyclase in the cell membrane?Nephrogenic diabetes insiptus (ADH unresponsive)
Failure of fetal endocrine fxn → Who does this happen in & why?Can happen bc of PROLONGED GESTATION in ruminants
Adenohypohyseal aplasia/hypoplasia in bovine → Synthesis defect. Explain what is happeningSeen as a genetic defect in Guernsey & Jersey cattle
Results in hypoplasia of target organs
Cessation of fetal development after 7 months
Prolonged gestation ↓
Explain how a hypoplasia of a fetus can prolong pregnancyProlonged gestation in such cases is due to hypoplasia of the adrenal cortex leading to inadequate cortisol secretion & failure of induction of 17α-hydroxylase in placenta that converts progesterone to estrogen (the estrogen surge, when it occurs, stimulates PG synthesis in the uterus, which results in smooth muscle contractions & biochemical changes in collagen along the birth canal that normally permit delivery of the fetus).
Hypothalamic-Pituitary malformations in ovine → What plant czs this & what problems happen bc of it?Ingestion of the toxic plant Veratrum californicum by ewes in early pregnancy czs cranial malformation (cyclopia, CNS malformations, nasofacial defects) & aplasia/hypoplasia of the fetal pituitary; results in hypoplasia of target endocrine organs in the fetus & prolonged gestation, but the fetus will continue to grow
Explain how adenohypophyseal aplasia/hypoplasia leads to prolonged pregAdrenocortical hypoplasia → ↓ blood cortisol → Failure of induction of placental 17α-hydroxylase in the placenta that converts precursor molecules (e.g., progesterone) to estrogen → Lack of estrogen peak at term (so labor not on time)
↑ Degradation of hormone → Long-term administration of xenobiotics. Give an example of when this happensExtensive dosing of phenobarbital in lab rats induces hepatic enzymes (thyroxine uridine diphosphate glucuronyl transferase) which in turn ↑ the degradation of thyroxine, which leads to ↑ TSH secretion, which can lead to thyroid follicular cell neoplasms
↓ Degradation of hormone → Feminization due to hyperestrogenism. What can this be associated with?Cirrhosis, which means there is ↓ hepatic degradation of estrogens
**Chronic renal Dz in dogs occasionally is associated w/ persistent HyERrcalcemia why?Kidney is unable to degrade PTH (along w/ ↓ urinary excretion of Ca+ = ↑ PTH & ↑ Ca)
How can iatrogenic progesterone in dogs lead to Acromegaly? CS?Progesterone in dogs can induce growth hormone expression in mammary gland!
This can lead to acromegaly, which appears as:
Excessive skin folds
Respiratory stridor due to ↑ soft tissue in oropharyngeal region
Expansion of interdental spaces & hyperglycemia

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