Pathology-Endocrine Pathology Flashcards
A 43 year old woman comes to see the neurologist with recurrent headaches and bitemporal hemianopsia. Labs reveal decreased levels of FSH, LH, ACTH, TSH, PRL, and GH. What is causing her condition?
She has a benign non function (because it is not producing hormones) anterior pituitary adenoma. She has bitemporal hemianopsia because the lateral visual fields hit the nasal side of the retina and cross over the optic chiasm, which is being compressed by the adenoma.
A 43 year old woman comes to see you in clinic with galactorrhea and amenorrhea. What type of pituitary tumor could be causing her condition?
She has a prolactinoma, the most common anterior pituitary adenoma. Prolactin inhibits GnRH synthesis and release, which prevents release of FSH and LH, which results in amenorrhea in females. Prolactin also stimulates milk production.
A 43 year old male presents with decreased libido and headaches. He is diagnosed with a prolactinoma. Why does he not have galactorrhea?
Increased prolactin inhibits production and secretion of GnRH, inhibiting FSH and LH, decreasing his libido. He does not get galactorrhea because males only have a terminal duct and no lobular units in breast tissue. He also has a headache from mass effect.
A 43 year old male presents with decreased libido and headaches. He is diagnosed with a prolactinoma. How do you treat him?
Surgery or dopamine agonist (dopamine from the hypothalamus inhibits prolactin secretion, bromocriptine)
A mother with enlarged hands, feet, tongue and jaw brings in her 8 foot tall 20 year old son. What is the most common cause of death in these patients? What secondary condition is highly associated with their condition?
Growth hormone adenomas can cause enlargement of the heart and death from cardiac failure. The mother has acromegaly (adenoma during adulthood) and her son has gigantism (adenoma during childhood). Since GH suppressed insulin release, they often suffer from secondary diabetes.
A mother with enlarged hands, feet, tongue and jaw brings in her 8 foot tall 20 year old son. You suspect a growth hormone adenoma. How do you confirm the diagnosis?
Elevated GH and IGF-1 (production is increased by increased GH action on hepatocytes) in the serum. Also, giving oral glucose does not suppress GH levels.
What is the mediator of tissue growth?
IGF-1 from hepatocytes. GH stimulates increased levels of IGF-1.
A mother with enlarged hands, feet, tongue and jaw brings in her 8 foot tall 20 year old son. You suspect a growth hormone adenoma. How do you treat them?
Octreotide (somatostatin that blocks ant. pit. response to hypothalamic GHRH), surgery or GH receptor antagonists.
Pituitary adenoma that causes Cushing’s syndrome?
ACTH cell adenomas that secrete ACTH
Rare types of functional pituitary adenomas
TSH, LH and FSH-producing adenomas.
How long does it take for hypopituitarism to manifest?
Usually not until 75% of pituitary parenchyma is lost.
A 30 year old woman gives birth to a newborn baby. She comes in a few days later complaining that she is having a difficult time producing breast milk for the baby. On physical exam you note decreased pubic hair and when reviewing her history you note that there was significant blood loss on delivery. What is likely causing her condition?
Sheehan syndrome. During pregnancy the increased hormone levels cause the pituitary to double in size, with little change in blood supply. If significant blood loss occurs during labor, parts of the pituitary can infarct. She has trouble lactating due to decreased production of prolactin. She has loss of pubic hair because production is dependent on androgens, which is dependent on LH, which comes from the anterior pituitary.
A child presents with various symptoms consistent with hypopituitarism. Brain CT shows and empty sella turcica. What can cause this?
Damage to the pituitary that causes it to shrink and herniation of arachnoid or dura mater that pushes the pituitary up and out of the sella turcica.
2 types of tumors that can cause hypopituitarism
Pituitary adenoma and craniopharyngioma (from Rathke’s pouch).
A patient comes to the ED after a car accident and is suffering from central diabetes insipidus due to pituitary damage. What symptoms would you expect him to present with?
Damage to either the hypothalamus or posterior pituitary causes decreased ADH release. This results in polyuria, polydipsia, hypernatremia, increased serum osmolality, low urine osmolality and low specific gravity because there is no Na or H2O reabsorption going on in the nephron.
A patient comes to the ED after a car accident and is suffering from central diabetes insipidus due to pituitary damage. How do you confirm your diagnosis? How do you treat?
Water deprivation test fails to increase urine osmolality. You treat him with desmopressin (an ADH analogue)
A patient comes to the ED with polyuria, polydipsia, hypernatremia and decreased urine osmolality. He fails to respond to the water deprivation test and to desmopressin. What could be causing his condition?
Since he didn’t respond to desmopressin, you know it is nephrogenic diabetes insipidus. Impaired renal response to ADH can be caused by inherited mutations or drugs (lithium or demeclocycline)
A patient presents after a seizure with hyponatremia and low serum osmolality. His condition is improved with free water restriction and demeclocycline. What is causing his condition?
SIADH. Increased ADH levels increases Na and H2O retention. He had a seizure because hyponatremia causes swelling of the nerves and cerebral edema. Water restriction will decrease the blood volume and demeclocycline will decrease renal response to ADH
A patient presents after a seizure with hyponatremia and low serum osmolality. His condition is improved with free water restriction and demeclocycline. What are common etiologies of this condition?
Ectopic ADH production (small cell lung cancer), CNS trauma, pulmonary pathology/infection and drugs (cyclophosphamide) can all cause SIADH.
Cysts of thyroid tissue in the anterior midline of the neck
Thyroglossal duct cyst
Persistence of thyroid tissue at base of tongue
Lingual thyroid
Why do people with hyperthyroidism lose weight?
Increased levels of thyroid hormone increases synthesis of Na/K ATPase and increases energy requirements.
Why do people with hyperthyroidism have increased pulse pressure?
Increased levels of thyroid hormone increased expression of beta-1 adrenergic receptors, activating the sympathetic nervous system and increasing the systolic blood pressure.
Signs and symptoms of hyperthyroidism
“Thyroidism” Tremor, HR increase, Yawning (fatigue), Restlessness, Oligomenorrhea, Intolerance to heat, Diarrhea, Irratibility, Sweating, Muscle wasting & weight loss, Exopthalmos
What happens to blood calcium, cholesterol and glucose levels in people with hyperthyroidism?
Hypercalcemia from increased bond resorption, hypocholesterolemia and hyperglycemia (from activation of gluconeogenesis and glycogenolysis by thyroid hormone).
What is the most common cause of hyperthyroidism, which occurs in women of childbearing age?
Graves disease. IgG autoantibodies stimulate TSH receptors and increases synthesis and release of thyroid hormone.
A 30 year old woman presents with a diffuse goiter, exopthalmos and pretibial myxedema. Labs reveal elevated IgG antibodies. What is causing her exopthalmos and pretibial myxedema?
The IgG autoantibodies stimulate TSH receptors on fibroblasts behind the eye and on the shin. This causes them to increase production of glycosaminoglycans, which will give the tissue on the shin a “dough-like” consistency. This will also cause the eyes to be pushed forward.
This is a section from a patient who has a diffuse goiter from Graves disease. What would you expect histological examination of this tissue to look like?
TSH stimulation causes enlargement of the follicles due to increased thyroid hormone production. It also causes scalloping around the follicle due to increase thyroid hormone release from the colloid.
A 30 year old woman presents with a diffuse goiter, exopthalmos and pretibial myxedema. What labs would you expect to find?
Increased total and free T4, decreased TSH (T4 negative feedback down regulates TRH receptors on anterior pituitary), hypocholesterolemia and increased serum glucose.
A 30 year old woman presents with a diffuse goiter, exopthalmos and pretibial myxedema. How do you treat her?
Beta-blockers to decrease sympathetic activation, thioamides (blocks peroxidase conversion of iodide to iodine, addition of DIT/MIT to thyroglobulin and production of T3 & T4 thyroglobulin) and radio iodine ablation.
After delivering a baby C-section, the mother has an arrhythmia, hyperthermia, vomiting and hypovolemic shock. No sign of hemorrhage is presents. Labs reveal high levels of T4. What is causing her condition and how do you treat her?
This is thyroid storm caused by elevated catecholamines and massive hormone excess due to a stress like childbirth or surgery, which she had both. You would treat her with PTU (inhibits peripheral conversion of T4->T3), beta-blockers and steroids.
What things do thioamides inhibit?
Oxidation, organification and coupling
A patient presents with a multi nodular goiter. What is the most common cause of this and what is the prognosis?
Most common cause is iodine deficiency. Typically it is non-toxic but rarely regions of the goiter can become TSH-independent (toxic goiter)
Clinical features of hypothyroidism in neonates and infants
Cretinism: mental retardation, short stature w/skeletal abnormalities, coarse facial features, enlarged tongue and umbilical hernia.
A child is born with mental retardation, short stature, skeletal abnormalities, coarse facial features, enlarged tongue and an umbilical hernia. What are possible etiologies of this condition?
This child has cretinism. This can be caused by maternal hypothyroidism during early pregnancy, thyroid agenesis, dyshormonogenetic goiter and iodine deficiency.
Most common enzyme disorder that causes cretinism in the neonate?
Thyroid peroxidase enzyme
Clinical features of hypothyroidism in older children and adults.
Myxedema, weight gain w/normal appetite, slowed mental activity, muscle weakness and cold intolerance w/decreased sweating.
Why do people with hypothyroidism sometimes present with a swollen tongue and deeper voice?
Low thyroid activity causes increased TSH secretion by the anterior pituitary. This also stimulates TSH receptors on fibroblasts in the tongue and larynx, causing tissue to grow.
Why do people gain weight w/normal appetite and hypothyroidism?
Decreased sympathetic activity.
A patient presents with a deepened voice, swollen tongue, weight gain w/normal appetite, slowed mental activity, muscle weakness and cold intolerance w/decreased sweating. What are possible etiologies of his condition?
This patient has hypothyroidism. Causes include iodine deficiency, Hashimoto thyroiditis (autoimmune destruction of thyroid gland), drugs (lithium), surgical removal of or radio ablation of the thyroid.
A patient presents with a deepened voice, swollen tongue, weight gain w/normal appetite, slowed mental activity, muscle weakness and cold intolerance w/decreased sweating. He is in the US, what is the most likely cause of his condition?
Hashimoto thyroiditis, associated with HLA-DR5. This is the most common cause of hypothyroidism where iodine levels are sufficient.
A patient presents with a deepened voice, swollen tongue, weight gain w/normal appetite, slowed mental activity, muscle weakness and cold intolerance w/decreased sweating. He is in the US. What labs would you expect to see in this patient?
Initial hyperthyroidism that progresses to hypothyroidism (leakage of already produced thyroid hormone from destruction of thyroid follicles), decreased T4, increased TSH and antithyroglobulin and antimicrosomal antibodies.
What causes increased production of TSH by the anterior pituitary when people have Hashimoto’s thyroiditis?
Decreased levels of T4 increases expression of TRH receptors on the anterior pituitary, allowing for increased stimulation from the hypothalamus and increased TSH production by the anterior pituitary.
What would you expect to see histologically in a patient with Hashimoto’s thyroiditis?
Abundant chronic inflammatory cells with germinal centers. Also Hurthle cells form (pink cells around follicles)
A patient presents with an enlarging thyroid gland who was diagnosed with Hashimoto’s thyroiditis. What cancer is he at increased risk for?
B-cell lymphoma. Germinal centers form in the thyroid, then marginal zones form where lymphoma develops.
A 30 year old woman presents with transient heat intolerance, anxiety and tremors after a viral infection. Physical exam reveals a tender thyroid. What is causing her condition?
Subacute (deQuervain) Granulomatous Thyroiditis. Granulomatous inflammation occurs in the thyroid after a viral infection, this condition does not progress to hypothyroidism and is self-limiting.
A 30 year old woman presents with wheezing, a 10 pound weight gain, fatigue, cold intolerance and muscle weakness. Physical exam reveals a thyroid gland that is hard as wood and contender. What is causing her condition?
Reidel Fibrosing thyroiditis. Chronic inflammation of the thyroid and extensive fibrosis in the thyroid cause the hard thyroid and hypothyroidism. Remember that fibrosis may extend to local structures (airway wheezing).
How do you differentiate anaplastic carcinoma of the thyroid from Reidel Fibrosing thyroiditis?
Carcinoma is a disease of older people that invades local structures like the airway. Reidel is a disease of younger people that invades local structures like the airway. Other than this, history will be similar.
When do you decide to biopsy a thyroid nodule?
Do an I-131 uptake scan. If there is uptake then it is a nodular goiter and does not need biopsy. If it is a “cold spot”, then it could be an adenoma (most likely) or a carcinoma and warrants a fine-needle aspiration (FNA) biopsy.
A patient presents with a thyroid nodule. I-131 uptake scan shows a cold spot. FNA is shown below. What is your diagnosis?
Follicular adenoma. Note the lower area with a dense pink capsule and proliferation follicle-like spaces.
4 types of thyroid carcinoma
Papillary (most common type), follicular, medullary and anaplastic.
Exposure to ionizing radiation in childhood puts you at risk for which type of thyroid carcinoma? What is the prognosis?
Papillary. Although this thyme often spreads to the cervical lymph nodes, prognosis is excellent.
Histologic features of papillary carcinoma
Orphan Annie eye nuclei, presence of nuclear grooves, formation of papilla and sometimes circular calcifications in papillae (psammoma bodies)
What differentiates a follicular adenoma from a follicular carcinoma? How do we obtain this differentiation?
Follicular carcinoma as a malignant proliferation of follicles surrounded by a fibrous capsule through which the malignant cells have invaded. You cannot see this through FNA, you must do an actual biopsy where you can analyze the tumor capsule.
A patient presents with hypocalcemia and a lump in her thyroid. What is most likely causing her condition and what would you expect to see histologically?
Medullary carcinoma, a malignant proliferation of parafollicular C cells that secrete high levels of calcitonin, causing hypocalcemia. On FNA you would see malignant cells in an amyloid stroma (high levels of calcitonin deposit as amyloid).
What would you expect to see on FNA in a patient with anaplastic carcinoma of the thyroid?
Highly malignant cells from FNA of the thyroid.
What causes this condition in the renal biopsy shown below from a patient with primary hyperparathyroidism?
Metastatic calcification from hypercalcemia causing nephrocalcinosis.
What causes this condition in the bone biopsy shown below in a patient with primary hyperparathyroidism?
Increased activation of osteoclasts causes fibrosis of the bone and osteitis fibrosa cystica.
Where are the insulin secreting cells located in the islets of Langerhans?
Beta cells are located in the center of the islets
How does early type II diabetes differ from late type II diabetes?
Early on insulin levels are increased. Later on beta-cell exhaustion leads to insulin deficiency (note islets full of amyloid).
How does diabetes injure the kidney?
Preferential hyaline atherosclerosis of the efferent arteriole increases the glomerular filtration pressure and you get hyper filtration injury. Initially you will get microalbuminuria, then you get glomerular sclerosis in the mesangium (Kimmelstein-Wilson nodules) and nephrotic syndrome. As hyaline arteriolosclerosis progresses to the afferent arteriole you get decreased glomerular filtration and progression to diffuse sclerosis of the glomerulus and chronic renal failure.
A mother gives birth to a set of twins. Early on the boy has precocious puberty and the girl has clitoral enlargement. They are brought to the ED because of life-threatening hypotension. Labs reveal a decreased level of cortisol in the blood, hyponatremia and hyperkalemia. What is causing their condition?
They have Congenital Adrenal Hyperplasia (CAH) from deficiency in the enzyme 21-hydroxylase. This causes increased synthesis of androgens (clitoral enlargement and precocious puberty), cortisol deficiency (life-threatening hypotension and bilateral enlarged adrenal glands from ACTH stimulation) and mineralocorticoid deficiency (lack of aldosterone causes hyponatremia and hyperkalemia)
A mother gives birth to a set of twins. Early on the boy has precocious puberty and the girl has clitoral enlargement. They are brought to the doctor because of enlarged adrenal glands on incidental imaging. Labs reveal a decreased level of cortisol. What is causing their condition?
The have an 11-hydroxylase deficiency. This causes cortisol deficiency (hypotension and bilaterally enlarged adrenal glands) and increased androgens (precocious puberty and clitoral enlargement). Since 21-hydroxylase is still active and produce weakly active mineralocorticoids you don’t have the hyponatremia and hyperkalemia seen with 21-hydroxylase deficiency.
A mother brings in her kid because he had enlarged bilateral adrenal glands as an incidental finding on abdominal imaging. He is actually 16 but never hit puberty. Labs reveal hypernatremia and hypokalemia. What is causing his condition?
They have 17-hydroxylase deficiency. This causes cortisol deficiency (bilaterally enlarged adrenal glands) and androgen deficiency (late puberty). It also causes excess mineralocorticoids (hypernatremia and hypokalemia).
A young child presents with N. meningitis infection that progressed to DIC. What could exacerbate his condition?
Waterhouse-Friderichsen syndrome. This is central necrosis of the adrenal gland producing a “sac of blood” on biopsy. Adrenal insufficiency leads to hypotension on top of meningitis and DIC, complicating the condition.
A female presents complaining of episodic HTN, headaches, palpitations, tachycardia and sweating. She later dies of a heart attack and biopsy is shown below. What is your diagnosis?
Note that all of her symptoms are a result of increased EPI and NE. Note the brown tumor that is the same color as the medulla, classic of a medullary pheochromocytoma.
