Endocrine Disorders Flashcards
How common is a supernumerary parathyroid gland, and where is the supernumerary gland most likely to be found?
Incidence of up to 15%. Most often found in the thymus, thyrothymic tract and carotid sheath
Where do the superior and inferior parathyroid glands obtain their blood supply?
Most blood supply comes from inferior thyroid artery, occasionally the superior glands may get supply from superior thyroid artery in 15% of cases.
How can PTH levels be use intraoperatively to determine the completeness of a parathyroidectomy?
PTH has a half life of 2-5 minutes. PTH levels can be drawn from the patient before incision and then 5-10 minutes after excision. If there is at least a 50% decrease in the PTH level into the normal or near normal range, the excised gland was likely the offending gland.
What structures are landmarks in identifying the superior parathyroid gland?
80% of superior parathyroid glands are found on the posterior aspect of the thyroid gland within a 1cm diameter centered 1cm superior to the intersection of the RLN and inferior thyroid artery
What branchial pouch gives rise to the superior and inferior parathyroid glands
- 4th pouch gives rise to superior parathyroid gland and C cells
- 3rd pouch gives rise to inferior parathyroid gland and thymus
How does PTH maintain calcium levels?
PTH increases calcium absorption from the gut, mobilizes calcium from the bones, inhibits calcium excretion from the kidneys, and simulates renal hydroxylase to maintain activated vitamin D levels
What is the most potent regulator of PTH release?
serum calcium levels
Where are PTH receptors located and what downstream effects do they have in each location?
PTH binds to PTH receptors on bone and in the kidneys.
- PTH on osteoblasts case release of receptor activity of nuclear factor K ligand which then activates osteoclasts, which break down bone to increase serum calcium.
- In the kidney, PTH binds to renal tubule cells and induces reabsorption of calcium and decreases reabsorption of phosphate from the filtrate. It also induces the expression of an enzyme that converts the inactive form of vitamin D to the active form.
When monitoring total calcium levels in a patient what factor do you also need to note?
Albumin level
- Corrected calcium: (4-albumin level)0.8 + total calcium
What test results support the diagnosis of familial hypocalciuric hypercalcemia?
Hypercalcemia with 24 hr urinary calcium:creatine clearance ratio below 0.01, as well as one or more first degree relatives with hypercalcemia
Most common symptoms of chronic hypercalcemia?
“bones, stones, abdominal groans and psychiatric moans”
- renal calculi, bone pains, abdominal pains, depression, anxiety, cognitive dysfunction
Testing necessary to diagnose primary hyperparathyroidism?
Elevated albumin-corrected serum calcium or ionized calcium and elevated PTH
Most common cause of hypercalcemia in an outpatient setting?
Parathyroid adenoma
Most common cause of hypercalcemia in an inpatient setting?
Underlying malignancy
A patient has hypercalcemia and low or undetectable PTH levels. What is the likely diagnosis?
Paraneoplastic induced hypercalcemia mediated by PTH related protein. Primary hyperparathyroidism is ruled OUT by low PTH levels
What is the incidence of primary hyperparathyroidism in Western countries?
22: 100,000 persons per year. Incidence is higher in postmenopausal women
- Most cases occur in women (74%); incidence peaks in the 7th decade of life. Before age 45, incidence in men and women is similar.
What are the different types of parathyroid hyperplasia?
Parathyroid hyperplasia is predominantly caused by proliferation of chief cells within the gland. Rarely, water clear cell hyperplasia, which is a proliferation of vacuolated water clear cells, can be found. The water clear cell variant is clinically more severe and predominantly occurs in females.
Causative factors are associated with primary hyperparathyroidism?
- head and neck radiation in childhood
- long term lithium therapy
- genetic predisposition
Guidelines for surgical treatment in an asymptomatic patient with primary hyperparathyroidism?
- serum calcium > 1mg/dl above the upper limit of normal
- creatine clearance less than 60ml/min
- bone density T score less than -2.5 or previous fragility fracture
- Younger than 50
Typical laboratory values of calcium, PTH, and phosphate in secondary hyperparathyroidism
- low-normal calcium
- elevated PTH
- phosphate levels vary based on etiology (high in renal insufficiency, low in vitamin D deficiency)
Possible causes of secondary hyperparathyroidism
- Situations where low calcium levels triggers secretion of PTH and growth of parathyroid glands
- Renal failure (causes a decline in the formation of activated vitamin D and calcium absorption in the gut, impaired phosphate excretion all resulting in low calcium)
- Vitamin D deficiency
- Short gut syndrome or history of gastric bypass (risk of secondary disease resulting from malabsorption of both calcium and vitamin D)
Treatment of secondary hyperparathyroidism
- Correction of underlying cause
- Symptoms may improve with cincalcet or bisphosphates
- Role for subtotal parathyroidectomy if medical therapy fails
What is tertiary hyperparathyroidism?
A state of excess secretion of PTH after long standing secondary hyperparathyroidism. Phosphate levels in tertiary hyperparathyroidism are decreased. Renal dysfunction may lead to hyperphosphatemia despite elevated levels of PTH. Classic example is hyperparathyroidism persisting after renal transplantation.
Pathophysiology of tertiary hyperparathyroidism
Hypertrophied parathyroid glands become autonomous in their function and secrete PTH, leading to hypercalcemia despite withdrawal of calcium and calcitriol. High calcium levels can cause diffuse calcinosis.
Treatment of tertiary hyperparathyroidism
Total parathyroidectomy with autotransplantation or subtotal parathyroidectomy (3 and 1/2 gland resection)
What are the components of hyperparathyroidism-jaw tumor syndrome
Recurrent parathyroid adenomas, fibro-osseous tumors of the mandible, Wilms tumors
How do symptoms of acute and chronic hypoparathyroidism differ?
- Acute: dramatic hypocalcemia and associated paresthesias, muscle spasms, tetany and seizures
- Chronic: gradual in onset and may not present until patient develops blurry vision from cataracts
Most common causes of hypoparathyroidism
- Iatrogenic (after surgery)
- Congenital (third and 4th arches fail to develop properly)
Histologic description of a parathyroid adenoma?
Hypercellular gland consisting of chief and oncocytic cells with decreased intercellular fat
What is the most sensitive imaging study for identifying location of a parathyroid adenoma?
- Technetium 99m sestamibi with single photon emission CT (SPECT)
- Ultrasound can be helpful but is highly user dependent
How frequently is primary hyperparthyroidism caused by a single adenoma vs four gland hyperplasia?
- A single parathyroid adenoma is the cause in 80-85% of cases
- 4 gland hyperplasia is cause in 10-15% of cases
- Other causes include double adenomas (5%)
- Parathyroid carcinoma (<1%)
What features of a patient with hypercalcemia and elevated PTH are more concerning for a parathyroid carcinoma compared with benign parathyroid adenoma?
- Palpable neck mass
- Markedly elevated serum calcium levels (>14)
- Markedly elevated PTH
- Concomitant renal and bone disease
- Symptoms consistent with severe hypercalcemia
- Evidence of invasions such as vocal cord paralysis due to involvement of RLN
What is the gross pathologic description of a parathyroid carcinoma compared with a benign adenoma?
- Benign adenomas are generally soft, round or oval and reddish brown
- Parathyroid carcinoma is frequently large, lobulated and firm to stony hard mass, with a grayish white capsule that is frequently adherent or invasive to surrounding tissues
What is the most common cause of death in patients with parathyroid carcinoma?
Patients often diet from the effects of excessive PTH secretion and uncontrolled hypercalcemia rather than growth from tumor mass.
From what brachial structures does the thyroid develop?
The thyroid develops from an endodermal diverticulum of the floor of the primitive pharynx. The medial primordia is derived from the first and second pharyngeal pouches. The lateral primordia is derived from the fourth and fifth pharyngeal pouches.
The ultimobranchial bodies develop into what structures?
The parafollicular (c cells) cells which release calcitonin - Develop from the 4th pharyngeal pouch neural crest cells
What is the most common pattern of descent of the thyroid gland in relation to the hyoid bone?
The thyroid gland descends anterior to the hyoid bone during gestational weeks 4-7
Most common location of ectopic thyroid tissue?
Base of tongue (lingual thyroid)
What does the proximal portion of the the thyroglossal duct form?
foramen cecum of the tongue
What does the caudal remnant of the thyroglossal duct form?
pyramidal lobe of the thyroid (present in 40-55% of patients
Most common path of right and left recurrent laryngeal nerves
- Right: wraps around and passes deep to the right subclavian artery, then travels in a more oblique path to enter the larynx just posterior to the cricothyroid joint
- Left: wraps around and passes deep to the arch of the aorta, then travels in a more medial path within the tracheoesophageal groove
What is the relationship of the RLN and the cricothyroid joint?
The RLN enters the larynx posterior to the cricothyroid joint
What does the external branch of the superior laryngeal nerve innervate?
cricothyroid muscle (increases pitch)
What does the internal branch of the superior laryngeal nerve innervate?
Provides sensation of the supraglottic structures and shares sensation of the glottis with the RLN
Where does the superior laryngeal nerve branch off from the vagus?
Immediately below the nodose ganglion (inferior ganglion) of the vagus nerve, located just inferior to the jugular foramen
What is the name of the prelaryngeal lymph node?
Delphian node
Boundaries of level VI cervical lymph nodes (central neck compartment)?
Hyoid superiorly, brachiocephalic vein inferiorly, carotid arteries laterally
What is the name of the naturally occuring thyroidal enlargement on the lateral portion of the thyroid gland?
The tubercle of Zuckerkandl
What is the name of the posterior suspensory ligament of the thyroid?
Berry ligmanent
Define the borders of Simon triangle
The space between the esophagus (tracheoesophageal groove) medially , the carotid laterally, and the inferior thyroid artery superiorly
Define the borders of the Joll triangle
The space between the inferior pharyngeal constrictor and the cricothyroid muscle medially, the sternothyroid muscle laterally, and the superior thyroid pole inferiorly
What is the active form of thyroid hormone?
T3. T4 must be deiodinated to T3 to act on peripheral tissue
Describe the internal regulatory pathway of thyroid hormogenesis
- Hypothalamus releases thyroid releasing hormone (TRH)
- TRH binds a receptor in the anterior pituitary that increases production and release of thyroid stimulating hormone (TSH)
- TSH stimulates release of stored T3 and T4, increases production of T3 in relation to T4, increases production of thyroglobulin and thyroperoxidase (TPO)
- Entire system is controlled by negative feedback loop
What is the Wolff-Chaikoff effect?
Describes the decreased thyroid hormone production as a result of excess iodine ingestion (such as Lugol iodine administration in patients with Graves disease)
What hormones are produced by the thyroid gland?
T3 and T4
What medications are the mainstay of treatment in the acute setting of thyroid storm?
- Propranolol to control tachyarrhythmias
- Methimazole to reduce thyroid hormone production
- An hour after methimazole has been given, potassium iodide can be given to decrease hormone release and vascularity of thyroid gland if surgery is considered
What are the key components of thyroid hormone?
Iodine and thyroglobulin