Endocrine Pathology Flashcards
PITUITARY ADENOMA
Types
How does each type present?
Benign tumor of anterior pituitary cells
- May be functional (hormone-producing) or nonfunctional (silent)
-
Nonfunctional tumors often present with mass effect:
i. Bitemporal hemianopsia occurs due to compression of the optic chiasm.
ii. Hypopituitarism occurs due to compression of normal pituitary tissue.
iii. Headache -
Functional tumors present with features based on the type of hormone produced.
- Prolactinoma
- Growth hormone cell adenoma
- ACTH cell adenoma
- TSH, LH, FSH producing are rare
Growth hormone cell adenoma
- presentation child vs. adult*
- Features*
- $ Condition commonly present?*
- How diagnosed?*
- $ Treatment*
- Gigantism in children-increased linear bone growth (epiphyses are not fused)
- Acromegaly in adults
- i. Enlarged bones of hands, feet, and jaw
ii. Growth of ,·isceral organs leading to drsfunction (e.g., cardiac failure)
iii. Enlarged tongue - $ Secondary diabetes mellitus is often present (GH induces liver gluconeogenesis).
- Diagnosed by elevated GH and insulin growth factor-1 (IGF-1) levels along with lack of GH suppression by oral glucose
- $ Treatment is octreotide (somatostatin analog that suppresses GH release), - Blocks effect of GHRH on AP and decreases GH
- GH receptor antagonists, or surgery.
HYPOPITUITARISM
$ Causes
$Presentation
Insufficient production of hormones by the anterior pituitary gland; symptoms arise when> 75% of the pituitary parenchyma is lost.
Causes:
- Pituitary adenomas (adults) or craniopharyngioma (children)-due to mass effect or pituitary apoplexy (bleeding into an adenoma)
-
_$ Sheehan syndrome-pregnancy-related infarction of the pituitary gland _i. Gland doubles in size during pregnancy, but blood supply does not increase significantly; blood loss during parturition precipitates infarction.
- $ Presents as poor lactation, loss of pubic hair, and fatigue
-
Empty sella syndrome - congenital defect of the sella - Herniation of the arachnoid and CSF into the sella compresses and destroys
the pituitary gland.
Poor lactation, loss of pubic hair, and fatigue after pregnancy
$ Why is Secondary diabetes mellitus often present in Growth hormone cell adenoma?
GH induces liver gluconeogenesis and also decreases glucose uptake by cells. Patients show lack of GH suppression by oral glucose.
ADH
Oxytocin
made in the hypothalamus and then transported via axons to the posterior pituitary for release.
- ADH - acts on the distal tubules and collecting ducts of the kidney to promote free water retention
- Oxytocin - mediates uterine contraction during labor and release of breast milk (let-down) in lactating mothers.
CENTRAL DIABETES INSIPIDUS
- Clinical features*
- Diagnosis*
- Treatment*
ADH deficiency - Due to hypothalamic or posterior pituitary pathology (e.g., tumor, trauma, infection,
or inflammation)
Clinical features are based on loss of free water.
- Polyuria and polydipsia with risk of life-threatening dehydration
- Hypernatremia and high serum osmolality
- Low urine osmolality and specific gravity
Water deprivation test fails to increase urine osmolality (useful for diagnosis).
Treatment is desmopressin (ADH analog)
NEPHROGENIC DIABETES INSIPIDUS
How does it differ from Central Diabetes Insipidus?
Impaired renal response to ADH - Due to inherited mutations or drugs (e.g., lithium and demeclocycline)
Clinical features are similar to central diabetes insipidus, but there is no response to desmopressin
SYNDROME OF INAPPROPRIATE ADH (SIADH) SECRETION
- Clinical features*
- Treatment*
Excessive ADH secretion - Most often due to ectopic production (e.g., small cell carcinoma of the lung);
other causes include CNS trauma, pulmonary infection, and drugs (e.g., cyclophosphamide).
Clinical features are based on retention of free water.
- Hyponatremia and low serum osmolality
- Mental status changes and seizures - Hyponatremia leads to neuronal swell ing and cerebral edema
Treatment is free water restriction or demeclocycline
Pathology of the posterior pituitary
CENTRAL DIABETES INSIPIDUS
NEPHROGENIC DIABETES INSIPIDUS
SYNDROME OF INAPPROPRIATE ADH (SIADH) SECRETION
Pathology of the ANTERIOR PITUITARY GLAND
PITUITARY ADENOMA
HYPOPITUITARISM
Overview of THYROID GLAND Pathology
- THYROGLOSSAL DUCT CYST
- LINGUAL THYROID
- HYPERTHYROIDISM - GRAVES DISEASE, MULTINODULAR GOITER
- HYPOTHYROIDISM - CRETINISM, MYXEDEMA
- THYROIDITIS - HASHIMOTO THYROIDITIS, SUBACUTE GRANULOMATOUS (DE QUERVAIN) THYROIDITIS, REIDEL FIBROSING THYROIDITIS
- THYROID NEOPLASIA - FOLLICULAR ADENOMA, PAPILLARY CARCINOMA, FOLLICULAR CARCINOMA, MEDULLARY CARCINOMA, ANAPLASTIC CARCINOMA
THYROGLOSSAL DUCT CYST
- Cause*
- $ Clincial presentation*
Cystic dilation of thyroglossal duct remnant - Thyroid develops at the base of tongue and then travels along the thyroglossal duct to the $ anterior neck. Thyroglossal duct normally involutes; a persistent duct, however, may undergo cystic dilation.
- $ Presents as an anterior neck mass
LINGUAL THYROID
Clinical presentation
Persistence of thyroid tissue at the base of tongue
$ Presents as a base of tongue mass
HYPERTHYROIDISM
Describe the basic principles of this state.
$What is the mechanism by which Thyroid hormone increases basal metabolic rate?
Increased level of circulating thyroid hormone
- Increases basal metabolic rate (due to increased synthesis of Na+ -K+ ATPase)
- Increases sympathetic nervous system activity (due to increased expression of Beta1- adrenergic receptors)
Clinical features of
HYPERTHYROIDISM
Clinical features include
- Weight loss despite increased appetite
- Heat intolerance and sweating
- Tachycardia with increased cardiac output
- Arrhythmia (e.g., atrial fibrillation), especially in the elderly
- Tremor, anxiety, insomnia, and heightened emotions
- Staring gaze with lid lag
- Diarrhea with malabsorption
- Oligomenorrhea
- Bone resorption with hypercalcemia (risk for osteoporosis)
- Decreased muscle mass with weakness
_**11. $ Hypocholesterolemia - $ Hyperglycemia (due to gluconeogenesis and glycogenolysis)**_
GRAVES DISEASE
Clincal features
Autoantibody (IgG) that stimulates TSH receptor (type II hypersensitivity) Leads to increased synthesis and release of thyroid hormone
- Most common cause of hyperthyroidism
- Classically occurs in women of childbearing age (20- 40 years)
Clinical features
- Hyperthyroidism
- Diffuse goiter-Constant TSH stimulation leads to thyroid hyperplasia and
hypertrophy -
_$ Exophthalmos and pretibial myxedema - _**_Fibroblasts behind the orbit and overlying the shin express the TSH receptor, _TSH activation results in glycosaminoglycan (chondroitin sulfate and
hyaluronic acid) buildup, inflammation, fibrosis, and edema leading to exophthalmos and pretibial myxedema.**
$ Pathogenesis of Exophthalmos and pretibial myxedema seen in Graves disease
Fibroblasts behind the orbit and overlying the shin express the TSH receptor.
- TSH activation results in glycosaminoglycan (chondroitin sulfate and hyaluronic acid) buildup, inflammation, fibrosis, and edema leading to exophthalmos and pretibial myxedema.
- NOT due to hyperthyroidism
- Myxedema - is edema due to myxoid (dough like) substance.
Histology seen in Graves disease?
Lab findings in Graves disease?
Irregular follicles with scalloped colloid and chronic inflammation are seen on histology
Lab findings:
- Increased total free T4, Decreased TSH (Free T4 downregulates TRH receptors in the AP to decrease TSH release)
- $ Hypocholesterolemia
- $ Increased serum glucose
Treatment for Graves disease
What is thyroid storm? Presents? How is it treated?
Treatment involves Beta -blockers, thioamide, and radioiodine ablation.
Thyroid storm is a potentially fatal complication.
l. Due to elevated catecholamines and massive hormone excess, usually in response to stress (e.g., surgery or childbirth)
2. Presents as arrhythmia, hyperthermia, and vomiting with hypovolemic shock
3. Treatment is propylthiouracil (PTU), p-blockers, and steroids.
_ $ PTU inhibits peroxidase-mediated oxidation, organification, and coupling steps of thyroid hormone synthesis, as well as peripheral conversion of T4 to T3_
MOA of Propylthiouracil (PTU)
** $ PTU inhibits peroxidase-mediated oxidation, organification, and coupling steps of thyroid hormone synthesis, as well as peripheral conversion of T4 to T3**
MULTINODULAR GOITER
Cause
Enlarged thyroid gland with multiple nodules - Due to relative iodine deficiency
- Usually nontoxic (euthyroid)
- Rarely, regions become TSH-independent leading to T1 release and hyperthyroidism (‘toxic goiter’).
CRETINISM
Clinical characteristics
What is TH needed for?
What causes cretinism?
Hypothyroidism in neonates and infants
Characterized by mental retardation, short stature with skeletal abnormalities, coarse facial features, enlarged tongue, and umbilical hernia
Thyroid hormone is required for normal brain and skeletal development.
Causes include maternal hypothyroidism during early pregnancy, thyroid agenesis, $dyshormonogenetic goiter and iodine deficiency.
Dyshormonogenetic goiter is due to a congenital defect in thyroid hormone production; most commonly involves THYROID PEROXIDASE
$ Dyshormonogenetic goiter
Dyshormonogenetic goiter is a cause of cretinism
Dyshormonogenetic goiter is due to a congenital defect in thyroid hormone production; most commonly involves THYROID PEROXIDASE
MYXEDEMA
Clinical features
Most common cause
Hypothyroidism in older children or adults
Clinical features are based on decreased basal metabolic rate and decreased sympathetic nervous system activity.
- Myxedema - accumulation of glycosaminoglycans in the skin and soft tissue; results in a_ $ deepening of voice and large tongue_
- Weight gain despite normal appetite
- Slowing of mental activity
- Muscle weakness
- Cold intolerance with decreased sweating
- Bradycardia with decreased cardiac output, leading to shortness of breath and fatigue
- Oligomenorrhea
- Hypercholesterolemia
- Constipation
Most common causes are iodine deficiency and Hashimoto thyroiditis; other causes include drugs (e.g., lithium) and surgical removal or radioablation of the thyroid.
HASHIMOTO THYROIDITIS
Clinical features
$ Histological findings
$ Risks
Autoimmune destruction of the thyroid gland; associated with HLA-DR5 - Most common cause of hypothyroidism in regions where iodine levels are
adequate
Clinical features
- Initially may present as hyperthyroidism (due to follicle damage)
- Progresses to hypothyroidism decreased T4, and increased TSH
- Antithyroglobulin and antimicrosomal antibodies are often present (sign of thyroid damage).
_$ Chronic inflammation with germinal centers and Hurthle cells (eosinophilic metaplasia of cells that line follicles) is seen on histology _
$ Increased risk for B-cell (marginal zone) lymphoma; presents as an enlarging thyroid gland late in disease course
SUBACUTE GRANULOMATOUS (DE QUERVAIN) THYROIDITIS
$ Presentation
Prognosis
Granulomatous thyroiditis that follows a viral infection
- Presents as a $tender thyroid with transient hyperthyroidism
- Self-limited; does not progress to hypothyroidism
REIDEL FIBROSING THYROIDITIS
Presentation
Complications
Mimics this disease. How are they different?
Chronic inflammation with extensive fibrosis of the thyroid gland
$ Presents as hypothyroidism with a ‘ hard as wood,’ nontender thyroid gland
_$ Fibrosis may extend to involve local structures (e.g., airway) _
$ Clinically mimics anaplastic carcinoma (patients usually in 70s), but patients are younger (40s), and malignant cells are absent. Classically a young female
42 yo Woman presents with symptoms of hypothyroidism with a ‘hard as wood’, nontender thyroid gland. Patient also notes slight difficulty breathing. Most likely diagnosis?
REIDEL FIBROSING THYROIDITIS
B. Presents as hypothyroidism with a ‘ hard as wood,’ nontender thyroid gland
C. Fibrosis may extend to involve local structures (e.g., airway).
l. Clinically mimics anaplastic carcinoma, but patients are younger (40s), and malignant cells are absent
A patient with a history of long-standing Hashimotos presents with an enlarged thyroid.
B-cell (marginal zone) lymphoma **- **presents as an enlarging thyroid gland late in disease course
THYROID NEOPLASIA
- What is used to futher characterize nodules. Explain.*
- $ How is biopsy performed?*
Usually presents as a distinct, solitary nodule - Thyroid nodules are more likely to be benign than malignant.
I-131 radioactive uptake studies are useful to further characterize nodules.
- Increased uptake (‘hot’ nodule) is seen in Graves disease or nodular goiter.
- Decreased uptake (‘cold’ nodule) is seen in adenoma and carcinoma; often warrants biopsy
$Biopsy is performed by fine needle aspiration (FNA)
FOLLICULAR ADENOMA
Benign proliferation of follicles surrounded by a fibrous capsule - Usually nonfunctional; less commonly, may secrete thyroid hormone
Most common Thyroid Cancers
2 FOLLICULAR CARCINOMA (10%)
#1 PAPILLARY CARCINOMA (70-85%)
“Paul Fifer Meets Ana”
PAPILLARY CARCINOMA
$ Major risk factor
$ Genetic mutation?
$ Histology
Lymphatic spread?
Prognosis
Most common type of thyroid carcinoma (80% of cases)
$Exposure to ionizing radiation in childhood is a major risk factor.
- $Most common mutation in the BRAF gene (serine/threonine kinase)
- $Commonly associated with rearrangements in RET oncogene or NTRK1
Comprised of papillae lined by cells with clear, ‘Orphan Annie eye’ nuclei and nuclear grooves papillae are often associated with _psammoma bodies _(concentric layers of calcification)
Often spreads to cervical (neck) lymph nodes, but prognosis is excellent (10-year survival> 95%)
FOLLICULAR CARCINOMA
Mutations
$ How is it distinguished from a follicular adenoma?
Metastasis
Prognosis?
Malignant proliferation of follicles surrounded by a _fibrous capsule with invasion through the capsule _
Second most common thyroid cancer (10%)
40% have RAS mutations
- Invasion through the capsule helps distinguish follicular carcinoma from follicular adenoma.
* *$2. Entire capsule must be examined microscopically.**
* *3. $ FNA only examines cells and not the capsule; hence, a distinction between follicular adenoma and follicular carcinoma cannot be made by FNA.**
$ Metastasis generally occurs hematogenously
Good prognosis
MEDULLARY CARCINOMA
$Biopsy Reveals?
$ What causes familial cases?
$ If a detection of this mutation is found, what is recommended?
Malignant proliferation of parafollicular C cells; comprises 5% of thyroid carcinomas - Calcitonin often deposits within the tumor as amyloid
$ Biopsy reveals sheets of _malignant cells in an amyloid stroma _
Familial cases are often due to multiple endocrine neoplasia (MEN) 2A and 2B, which are associated with mutations in the RET oncogene.
_1. MEN 2 results in medullary carcinoma, pheochromocytoma, and parathyroid
adenomas (2A) or ganglioneuromas of the oral mucosa (2B)._
$2. Detection of the RET mutation warrants prophylactic thyroidectomy.
MEN 2A vs MEN 2B
MEN 2 results in
- medullary carcinoma,
- pheochromocytoma, and
- parathyroid adenomas (2A) or ganglioneuromas of the oral mucosa (2B)
Papillary Carcinoma Histological Features
ANAPLASTIC CARCINOMA
$classically seen in?
Characteristics
Prognosis
Undifferentiated malignant tumor of the thyroid usually seen in elderly
- Often invades local structures, leading to dysphagia or respiratory compromise
- Poor prognosis
BASIC PRINCIPLES of Parathyroids
Which cells regulate free calcium? How? List 3 mechanisms
A. Chief cells regulate serum free (ionized) calcium via parathyroid hormone (PTH) secretion, which:
- Increases bone osteoclast activity (by activating osteblasts first), releasing calcium and phosphate
- Increases small bowel absorption of calcium and phosphate (ind irectly by
activating vitamin D) - Increases renal calcium reabsorption (distal tubule) and decreases phosphate reabsorption (proximal tubule)
B. Increased serum ionized calcium levels provide negative feedback to decrease PTH secretion.
PRIMARY HYPERPARATHYROIDISM
1 Cause PRIMARY HYPERPARATHYROIDISM
Most common cause is parathyroid adenoma (>80% of cases); sporadic parathyroid hyperplasia and parathyroid carcinoma are less common causes.
Parathyroid adenoma
Presentation
Parathyroid adenoma is a benign neoplasm (most common cause of primary hyperparathyroidism), usually involving one gland.
- Most often results in asymptomatic hypercalcemia; however, may present with consequences of increased PTH and hypercalcemia such as
i. Nephrolithiasis (calcium oxalate stones)
ii. Nephrocalcinosis- metastatic calcification of renal tubules (Fig. 15.9),
potentially leading to renal insufficiency and polyuria
iii. CNS disturbances (e.g., depression and seizures)
iv. Constipation, peptic ulcer disease, and $ acute pancreatitis
v. Osteitis fibrosa cystica - resorption of bone leading to fibrosis and cystic spaces (Fig. 15.10)
Lab findings in primary Hyperparathyroidism
Laboratory findings include
- Increased serum PTH,
- Increased serum calcium,
- Decreased serum phosphate,
- $ Increased urinary cAMP,
- $ Increased serum alkaline phosphatase - sign of osteoblast activity, PTH receptors on osteoblasts
Why is urinary cAMP elevated in Primary Hyperparathyroidism?
Why is serum alkaline phosphatase increased in Primary hyperparathyroidism?
$ Increased urinary cAMP - PTH receptor on tubular cells stimulates a G-stimulatory protein that activates Adenylate Cyclase converting ATP to cAMP that is released into the urine
$ Increased serum alkaline phosphatase - sign of osteoblast activity, PTH receptors on osteoblasts
SECONDARY HYPERPARATHYROIDISM
Excess production of PTH due to a disease process extrinsic to the parathyroid gland - Most common cause is chronic renal failure.
HYPOPARATHYROIDISM
Presentation
Labs
Low PTH - Causes include autoimmune damage to the parathyroids, surgical excision, and DiGeorge syndrome
Presents with symptoms related to low serum calcium
- Numbness and tingling (particularly circumoral)
- Muscle spasms (tetany)-may be elicited with filling of a blood pressure cuff (Trousseau sign) or tapping on the facial nerve (Chvostek sign)
Labs reveal decreased PTH levels and Decreased serum calcium.
$ Pseudohypoparathyroidism
$ Pseudohypoparathyroidism is due to end-organ resistance to PTH due to a defect in the G stimulatory protein that the PTH receptor uses.
$ 1. Labs reveal hypocalcemia with Increased PTH levels.
$ 2. Autosomal dominant form is associated with short stature and short 4th and 5th digits.
Patient complains of numbness and tingling with muscle spasm with filling of blood pressure cuff, Labs show elevated PTH. You note the patient has short stature and short 4th and 5th digits.
Pseudohypoparathyroidism is due to end-organ resistance to PTH. Labs will show elevated PTH and low serum calcium.
$ Where do beta cells lie?
Insulin is secreted by beta cells, which lie in the center of the islets
What characterizes type 1 DM?
Characterized by inflamma tion of islets
HLA-DR3 and HLA-DR4
Autoantibodies against insulin are often present (sign of damage) and may be
seen years before clinical disease develops.
Type IV hypersensitivity
Mechanism of resistance insulin resistance in DM II?
Genetics
Pancreatic histology?
Obesity leads to decreased numbers of insulin receptors.
Strong genetic predisposition exists.
Insulin levels are increased early in disease, but later, insulin deficiency develops due
to beta cell exhaustion; histology reveals amyloid deposition in the islets
Osmotic damage
- Glucose freely enters into Schwann cells (which myelinate peripheral nerves),** pericytes** of retinal blood vessels, and the lens.
- Aldose reductase converts glucose to sorbitol, resulting in osmotic damage.
- Leads to peripheral neuropathy, impotence, blindness, and cataracts; diabetes is the leading cause of blindness in the developed world.
PANCREATIC ENDOCRINE NEOPLASMS
Types?
$ How do you diagnose the first type?
Tumors of islet cells; account for < 5% of pancreatic neoplasms - Often a component of MEN I along with parathyroid hyperplasia and pituitary adenomas + pancreatic endocrine tumor
- Insulinomas present as episodic hypoglycemia with mental status changes that are relieved by administration of glucose - $ Diagnosed by decreased serum glucose levels (usually< 50 mg/dL), increased insulin, and increased C-peptide
- Gastrinomas present as treatment-resistant peptic ulcers (Zollinger-Ellison syndrome); ulcers may be multiple and can extend into the jejunum.
- Somatostatinomas present as achlorhydria (due to inhibition of gastrin) and cholelithiasis with steatorrhea (due to inhibition of cholecystokinin).
- VIPomas secrete excessive vasoactive intestinal peptide leading to watery diarrhea, hypokalemia, and achlorhydria.
HYPERCORTISOLISM (CUSHING SYNDROME)
Clinical features
Diagnosis
4 Major causes
Excess cortisol
Clinical features
- Muscle weakness with thin extremities-Cortisol breaks down muscle for gluconeogenesis.
- Moon facies, buffalo hump, and truncal obesity-High insulin (due to high glucose) increases storage of fat.
- Abdominal striae-due to impaired synthesis of collagen with thinning of skin
- Hypertension
- Osteoporosis
- Immune suppression
Diagnosis is made by increased 24-hour urine cortisol levels.
- Exogenous corticosteroids- leads to bilateral adrenal atrophy; steroids suppress ACTH secretion (negative feedback).
- Primary adrenal adenoma, hyperplasia, or carcinoma- leads to atrophy of the uninvolved adrenal gland
- ACTH-secreting pituitary adenoma-leads to bilateral adrenal hyperplasia
- Para neoplastic ACTH secretion (e.g., small cell carcinoma of the lung)-leads to bilateral adrenal hyperplasia
Why is cortisol an immunosuppresant?
- Cortisol induces the synthesis of lipocortin which inhibits phospholipase A2 preventing production of arachadonic product pathway
- Inhibits IL-2
- Inhibits the release of histamine and serotonin from mast cells and platelets
What is the purpose of the High-dose dexamethasone test?
High-dose dexamethasone (cortisol analog) suppresses ACTH production by a** pituitary adenoma** (cortisol levels decrease), but fails to suppress ectopic ACTH
production by a small cell lung carcinoma (cortisol levels remain high).
HYPERALDOSTERONISM (CONN SYNDROME)
Presentation
Why are these electrolyte stats seen regarding potassium, sodium, and acid-base status?
Excess aldosterone
Presents as hypertension with hypernatremia, hypokalemia, and metabolic alkalosis
- Aldosterone increases sodium absorption and secretion of potassium and hydrogen ions (distal tubules and collecting duct).
- Increased absorption of sodium expands plasma volume leading to hypertension.
HYPERALDOSTERONISM Types
How are these 2 types different?
Primary - #1 adrenal adenoma, LOW renin
Secondary - Activation of RAAS and HIGH renin
Primary hyperaldosteronism is most commonly due to an adrenal adenoma; sporadic adrenal hyperplasia and adrenal carcinoma are less common causes.
Characterized by high aldosterone and $low renin (high blood pressure downregulates renin via negative feedback)
Secondary hyperaldosteronism is seen with activation of the renin-angiotensin system (e.g., renovascular hypertension or CHF).
Characterized by high aldosterone and $ high renin
CONGENITAL ADRENAL HYPERPLASIA
What is the mechanism of adrenal hyperplasia?
Clinical features
Excess sex steroids with hyperplasia of both adrenal glands -_ Inherited 21-hydroxylase deficiency_ is the most common cause.
Deficiency of cortisol leads to increased ACTH secretion (lack of negative feedback), which results in bilateral adrenal hyperplasia.
Clinical features include
- Salt wasting with hyponatremia, hyperkalemia, and hypovolemia due to lack of aldosterone.
- Life-threatening hypotension due to lack of cortisol.
- Clitoral enlargement (females) or precocious puberty (males) due to excess androgens
ADRENAL INSUFFICIENCY
2 types and characteristics of each?
Causes
Lack of adrenal hormones
Acute insufficiency may arise with Waterhouse-Friderichsen syndrome - Characterized by $hemorrhagic necrosis of the adrenal glands, classically due to DIC in young children with N meningitidis infection. Lack of cort isol exacerbates hypotension, often leading to death.
Chronic insufficiency (Addison disease) is due to progressive destruction of the
adrenal glands.
1. Common causes include autoimmune destruction (most common cause in the West), TB (most common cause in the developing world), and metastatic carcinoma (e.g., arising from lung, LUNG CANCER LOVES ADRENAL).
2. Clinical features include hypotension, hyponatremia, hypovolemia, hyperkalemia, weakness, hyperpigmentation (increased ACTH by-products stimulate melanocytic production of pigment), vomiting, and diarrhea.
ADRENAL MEDULLA
Composed of neural crest-derived chromaffin cells. Main physiologic source of catecholamines (epinephrine and norepinephrine)
PHEOCHROMOCYTOMA
Clinical features
Diagnosed
Tumor of chromaffin cells
Clinical features are due to increased serum catecholamines - Episodic hypertension, headache, palpitations, tachycardia, and sweating
Diagnosed by increased serum metanephrines and increased 24-hour urine metanephrines and vanillylmandelic acid
VHL gene associated with an increased risk for these cancers
- Hemangioblastoma of cerebellum
- RCC
- Pheochromocytoma
Rule of 10s in pheochromocytoma
Associations of pheochromocytoma
Often follows the ‘rule of lOs:’ 10% bilateral, 10% familial, 10% malignant, and 10% located outside of the adrenal medulla (e.g., bladder wall or organ of Zuckerkandl at
the inferior mesenteric artery root)
Associated with MEN 2A and 2B, von Hippel-Lindau disease, and neurofibromatosis type 1
Pseudohypoparathyroidism type 1a
**Albright’s hereditary osteodystrophy **
- the result of defective Gs protein in kidney and bone, which causes end-organ resistance to PTH
- Hypocalcemia and hyperphosphatemia occur (as in hypoparathyroidism), which are not correctable by administration of exogenous PTH
- Circulating PTH levels are elevated (stimulated by hypocalcemia)
Diagnosis
15.4 Classic Waterhouse-Friderichsen syndrome - sac of blood in adrenal
Pathogenesis
Amyloid in islets, type II DM - beta cell exhaustion
Diagnosis
Pheochromocytoma - classic finding is brown tumor
Complication of what disease? Pathogenesis?
Hyaline Arteriolosclerosis - Complications of diabetes, Non-enzymatic glycosylation of small vessels (arterioles)
Pathogenesis
Glomerulosclerosis - Non Enzymatic glycosylation of renal arterioles is MOA - small scarred kidneys with granular surface
Pineal gland
Most common type of tumors
- midline above quadrigemmal plate
- Site for melatonin production
- commonly undergoes dystrophic calcification
- majority are germ cell tumors
- paralysis of upward gaze (“setting sun” sign)
Rathke’s pouch
an ectodermal derivative derived from the oral cavity. It develops into the anterior lobe of the pituitary gland.
Pituitary apoplexy
hemorrhage into preexisting adenoma
Often associated with women who are obese and have high blood pressure
Empty sella syndrome:
most common pituitary tumor
Prolactinoma
most common cause of
acute adrenocortical insufficiency
Most common cause of Addison’s disease in children
adrenogenital syndrome
diffuse hyperpigmentation;
hypotension, weakness
Addison’s disease
child with abdominal mass + hypertension
Neuroblastoma
