Endocrine Diseases and Tumors Flashcards
A 38-year-old female patient presents with a complaint of abdominal weight gain and weakness in the shoulders and hip girdle. She denies the use of any corticosteroid therapies. Nighttime salivary cortisol and low-dose dexamethasone suppression test are positive and serum adrenocorticotropic hormone (ACTH) is elevated.
A high-dose dexamethasone suppression test fails to suppress ACTH level. What is the next best step?
Choices:
1. Adrenal vein sampling
2. Evaluate for a primary malignancy producing ectopic ACTH
3. Head computed tomography scan
4. Corticotropin-releasing hormone (CH) stimulation test
Answer: 2 - Evaluate for a primary malignancy producing ectopic
ACTH
Explanations:
•The next best step is to search for primary malignancy. Secondary hypercortisolism via ectopic ACTH production may be observed in paraneoplastic Cushing syndrome in small cell lung cancer, renal cell carcinoma, and carcinoid syndrome.
• Ectopic ACTH secreting foci such as in paraneoplastic syndromes are resistant to negative feedback provided by the high-dose dex-amethasone suppression test, and cortisol level remains elevated.
• The high-dose dexamethasone suppression test should suppress
ACTH secretion in cases when low doses of dexamethasone fail to suppress it. If the cortisol level decreases after a high-dose dexam-ethasone suppression test, head imaging studies should be done to evaluate for pituitary adenoma (Cushing disease).
• If ACTH levels were low with positive nighttime salivary cortisol and low-dose dexamethasone suppression test, suspect adrenal overproduction of cortisol. evaluation.
StatPearls
A 3-year-old male is noted to have a 2 cm mass over the thyroid cartilage that the parent’s report has not changed for several months. The child has been healthy but is obese with weight at the 95th percentile and height at the 10th percentile. The thyroid gland is not palpable, and the rest of the exam is normal. What is the next step in evaluation?
Choices:
1. Thyroid-stimulating hormone (TSH) level
2. Fine needle aspiration cytology
3. Head and neck magnetic resonance imaging
4. Thyroid assessment with technetium-99m pertechnetate
Answer: 1 - Thyroid-stimulating hormone (TSH) level
Explanations:
• The child may have ectopic sub-hyoid thyroid tissue. TSH is an essential tool to evaluate for the diagnosis, especially when the patient is obese and short which indicates the underlying endocrinology issue.
• The normal thyroid function and the absence of manifestations in ectopic thyroid could last up to years.
•After establishing the diagnosis of hypothyroidism when the suspicion of ectopic thyroid is high, a radionuclide thyroid imaging employing technetium-99m pertechnetate is to be performed.
•The most common location of ectopic thyroid tissue is at the foramen cecum, resulting in a lingual thyroid.
StatPearls
Which one of these genes is involved in the pathogenesis of multiple endocrine neoplasia type II?
A APC
B p53
C RET
D VLH
E None of the above
C
Multiple endocrine neoplasia syndromes are inherited in an autosomal dominant pattern with very high penetrance.
The genetic defect in these disorders involves the RET proto-oncogene, a tyrosine kinase receptor, on chromosome 10q11.2.
All clinical manifestations of the multiple endocrine neoplasia type 2 (MEN-2) syndromes relate to a defect in transduction of growth and differentiation signals in several developing tissues that express RET.
So far, mutation analysis in MEN-2 families has identified over 50 different mutations related to the disease.
SPSE 1
Which of the following is not true regarding hypothyroidism in children?
A Thyroid-stimulating hormone (TSH) is elevated.
B Patients are usually symptomatic at birth.
C It can present as a sublingual mass.
D It is congenital in 90% of cases.
E Surgical treatment is rarely required.
B
Children may be rarely afflicted with acquired or congenital diseases of thyroid hormone production, resulting in either increased or decreased hormone production and secretion.
Thyroid gland dysgenesis is the most common cause of hypothyroidism diagnosed in neonatal screening programmes, accounting for approximately 90% of these patients.
In about one-third of these babies, no thyroid tissue is seen on radionuclide scanning.
In the rest of the patients, a rudimentary gland may be found in an ectopic location, usually the base of the tongue.
Often, there has been enough transplacental thyroid hormone present throughout development so even children with complete thyroid agenesis are asymptomatic at birth.
In some cases, ectopically located thyroid tissue may supply a sufficient amount of thyroxin for many years or may fail in childhood. This condition can be identified with the development of a sublingual or midline neck mass.
When evaluating neck masses in children, attention should be paid to this fact and a radionuclide thyroid scan should be considered, prior to removing any unusual neck mass. This will ensure that functioning thyroid tissue is not accidentally resected.
Because of its sensitivity, TSH is the best screening method for this condition.
Disorders of hypothyroidism are rarely treated surgically, and may result from a defect anywhere in the hypothalamic–pituitary–thyroid axis.
SPSE 1
Which of the following is not true about Graves’ disease?
A It is the most common cause of hyperthyroidism in childhood.
B Infection may elicit the production of autoantibodies against the TSH receptor.
C The condition is seen in girls about five times more than in boys.
D The condition is more frequent in the adolescent years.
E The congenital form occurs in 20% of infants born to mothers with active Graves’s disease.
E
Graves’s disease is the most common cause of hyperthyroidism in childhood.
It is characterised by autoimmunity by thyroid-stimulating antibodies that result in activation of thyrotropin receptors leading to unregulated hyperthyroidism.
This is mediated by immunoglobulins of the IgG class, and is present in 95% of the patients.
The event that initiates the production of these antibodies is unknown, but it has been postulated that it could be related to infection.
This is suggested by the presence of TSH-binding sites in gram-negative and gram-positive bacteria and also by epidemiologic reports of disease clustering.
The disease is seen in girls 5 times more than boys, and is higher in the adolescent population.
Congenital Graves’s disease occurs in 1% of infants born to women with active disease.
SPSE 1
While evaluating an infant on rounds, you notice that his mother looks anxious, complains of fatigue and heat intolerance, and admits to some weight loss despite having an increased appetite. You examine her carefully and discover that she is tachycardic, with a tremor. Furthermore she has fullness in her neck and in her eyes. She denies prenatal care. The infant is most likely at risk for development of:
A constipation
B heart failure
C macrocephaly
D third-degree heart block
E thrombocytosis.
B
The infant is likely at risk for neonatal thyrotoxicosis.
Neonatal thyrotoxicosis usually disappears within 2–4 months as the concentration of thyroid-stimulating immunoglobulin (TSI) diminishes.
Unlike TSI, TSH does not cross the placenta.
All forms of thyrotoxicosis are more common in females, with the exception of neonatal thyrotoxicosis, which has an equal sex distribution.
Symptoms include tachycardia and tachypnoea, irritability and hyperactivity, low birthweight with microcephaly, severe vomiting and diarrhoea, thrombocytopenia, jaundice, hepatosplenomegaly and heart failure.
In severely affected infants, the disease could be fatal if not treated vigorously and promptly.
Third-degree heart block is not a feature of this disease, but is sometimes seen in infants born to mothers with systemic lupus erythematosis.
SPSE 1
A 16-year-old female has had elevated serum calcium levels since birth. During her workup she is found to have a normal parathormone (PTH) level and hypocalciuria. She denies any symptoms. What would be the most appropriate treatment?
A 3½ parathyroidectomy
B technetium-99m sestamibi scintigraphy
C bisphosphonate
D observation
E single adenoma parathyroidectomy
D
The case describes a patient with familial hypocalciuric hypercalcaemic disease.
It is an autosomal dominant disease that expresses itself as an error in the calcium-sensing receptor. This results in higher-than-normal serum calcium levels.
These patients are usually asymptomatic and laboratory findings include hypercalcaemia, hypocalciuria and normal or slightly elevated PTH levels.
The diagnosis of familial hypocalciuric hypercalcaemia can be made by measuring urine calcium levels, which are lowered in these patients.
It is important to exclude this diagnosis in all patients with high serum calcium.
The treatment of this disease is strictly observational. Patients do not require surgery or further workup.
SPSE 1
What is the most common cause of primary hyperaldosteronism in children?
A Conn’s syndrome
B adrenocortical hyperplasia
C adrenocortical carcinoma
D Bartter’s syndrome
E none of the above
B
Overproduction of aldosterone is known as primary hyperaldosteronism when the cause is related to adrenal dysfunction.
This hypersecretion may be the result of bilateral nodular hyperplasia, or from an adrenocortical tumour (adenoma or carcinoma).
Adrenocortical hyperplasia is the most common cause in the paediatric population.
Children present with hypertension, hypokalaemia, elevated plasma aldosterone levels, and low plasma renin activity.
Children with hyperplasia are treated medically with spironolactone, an inhibitor of aldosterone biosynthesis, which is usually quite effective in managing the hypertension.
Bilateral adrenalectomy has not always been effective in curing the hypertension associated with this condition.
Bartter’s syndrome is a renal tubular defect that is characterised by hypochloraemic metabolic alkalosis, hypokalaemia, elevated urinary chloride, potassium and prostaglandin levels.
Patients have normal blood pressure, but hyperreninaemia and hyperaldosteronism are present.
SPSE 1
A 5-year-old male is referred to your clinic after presenting with a few months of muscle weakness, polydipsia and polyuria. His BP is 150/80. What is the next step in management?
A head CT scan
B aldosterone level
C potassium level
D check a renin level
E arterial blood gas
C
Signs and symptoms of primary hyperaldosteronism are non-specific. Children usually present with hypertension, muscle weakness, polydipsia and polyuria.
Constant high levels of aldosterone causes the total body sodium level to increase, thus increasing the total fluid volume.
This also suppresses renin and angiotensin.
When a child presents with hypertension and hypokalaemia, one should consider a diagnosis of primary hyperaldosteronism.
This is the reason why potassium levels are the initial screening test in children with hypertension.
SPSE 1
A 5-year-old male is referred to your clinic after presenting with a few months of muscle weakness, polydipsia and polyuria. His BP is 150/80. Potassium levels show hypokalemia.
CT scan shows no discrete masses. What is the next step in management?
A exploratory laparotomy
B selective adrenal vein sampling
C MRI scan
D abdominal ultrasonography
E none of the above
B
Once the diagnosis of hyperaldosteronism is confirmed, one has to distinguish between an adenoma and bilateral adrenal hyperplasia.
If a mass greater than 1 cm is identified by a CT scan or an MRI, the diagnosis of adenoma is entertained.
If no masses are visualised, a selective adrenal vein sampling can differentiate unilateral vs. bilateral adrenocortical hypersecretion.
SPSE 1
Which of the following is true about goitres in children?
A Most are euthyroid, and surgery is rarely indicated.
B With simple colloid goitre, the patient is hyperthyroid.
C Exogenous thyroid hormone is the treatment of choice for simple goitres D Graves’s disease is the most common cause.
E None of the above.
A
Diffuse thyroid enlargement can be due to a defect in hormone production, autoimmune disease or a response to an inflammatory condition.
Most children with goitres are euthyroid and surgical indication is rarely indicated.
The most common diagnosis of enlarged thyroid is simple goitre.
Other diagnoses include chronic lymphocytic thyroiditis, Graves’s disease, benign adenomas, and cysts.
Exogenous thyroid hormone does not enhance resolution of the goitre.
SPSE 1
Which of the following is not a manifestation or associated condition of Graves’s hyperthyroidism in children?
A Addison’s disease
B diffuse goitre
C ophthalmopathy
D diffuse arthropathy
E localised dermopathy
D
Graves’s disease is characterised by autoimmunity by thyroid-stimulating antibodies that results in activation of thyrotropin receptors leading to unregulated hyperthyroidism.
It is the most common cause of hyperthyroidism in children.
The clinical manifestations specific to Graves’s disease include diffuse goitre, exophthalmos, dermopathy and lymphoid hyperplasia.
Common diseases associated with Graves’ are diabetes mellitus, Addison’s disease, vitiligo, pernicious anaemia, myasthenia gravis, alopecia areata and other autoimmune diseases.
Patients will often present with signs and symptoms of hyperthyroidism.
Most children with Graves’s disease have a family history of some type of autoimmune thyroid disease.
SPSE 1
A 7-year-old obese female presents to your clinic with growth failure.
Which is the most sensitive test to order in this patient to screen for Cushing’s syndrome?
A high-dose dexamethasone suppression test
B 24-hour urine free cortisol
C adrenocorticotropic hormone (ACTH) stimulation test
D corticotropin-releasing hormone (CRH) test
E plasma cortisol level
B
The most sensitive and specific test to determine hypercortisolism is the 24-hour urine free cortisol test.
This avoids the episodic nature of cortisol secretion.
ACTH level can be elevated, suppressed or normal in hypercortisolism.
The CRH test is used to differentiate between a pituitary cause for hypercortisolism and other causes.
The high-dose dexamethasone test separates a pituitary source of hypercortisolism from an ectopic source of ACTH.
The ACTH stimulation test is used to determine the function of the adrenal gland(s) and is the test of choice to diagnose adrenal insufficiency.
The low-dose dexamethasone suppression test is used to diagnose hypercortisolism.
Although plasma ACTH level will most likely be elevated in adrenal insufficiency, this test is not specific for this condition.
Random serum cortisol levels are quite variable because of the episodic nature of cortisol secretion, and thus this test is not sensitive enough for diagnosing adrenal insufficiency.
SPSE 1
Non-endocrine manifestations of MEN2B include all the following, except:
A megacolon
B lichen amyloidosis
C mucosal neuromas
D hypertrophied corneal nerves
E pectus excavatum.
B
MEN syndromes are a group of endocrine disturbances that affect hormonesecreting glands. These are rare autosomal dominant conditions that predispose affected individuals to benign and malignant tumours of the pituitary, thyroid, parathyroids, adrenals, endocrine pancreas, paraganglia or non- endocrine organs.
The classic MEN syndromes include MEN type 1 (MEN-1) and MEN type 2 (MEN-2).
MEN-2 syndrome is often first suspected when a patient is found to have one or more of the tumours described in the syndrome, usually medullary thyroid cancer, or a family history.
These syndromes are accompanied by a series of non-endocrine manifestations that help in the diagnosis, especially in children with no known family history of the disease.
Cutaneous lichen amyloidosis is a component of the MEN-2A syndrome that has been described in families with the disease. It can be present before the onset of medullary thyroid carcinoma , and the identification of this skin lesion should prompt an evaluation for MEN-2A. The skin lesion is usually described as as intensely pruritic, red-brown hyperkeratotic papules most commonly seen in the interscapular region or on the extensor surfaces of the extremities. The first early symptom is usually pruritus; the amyloid deposition is seen later and is thought to be secondary to repeated scratching.
Amyloid deposition has been documented histologically.
MEN-2B presents with mucosal neuromas, intestinal ganglioneuromas and marfanoid habitus. Clinically the neuromas present in the tongue, lips and eyelids, with characteristic facial features including enlarged lips, a ‘bumpy’ tongue, and eversion of the eyelids. The marfanoid body habitus physic is accompanied by increased joint mobility and decreased subcutaneous fat.
Ganglioneuromatosis presents with thickening of the corneal nerves or in the gastrointestinal tract, resulting in abdominal distension, megacolon, constipation, or diarrhea.
All these physical traits are usually evident in early childhood, and are sometimes already present at birth.
SPSE 1
You are evaluating an 8-year-old female who complains of short stature. She is in the 10th percentile for her age. On further questioning, you notice that she had vaginal spotting for the last couple of months and she is also constipated. Her school performance has changed. On examination, she seems overweight and has a puffy face; no obvious masses are palpated on her neck, and she has muffled heart sounds. Which of the following conditions is most likely to present with these findings?
A rickets
B scurvy
C hypothyroidism
D microcytic anaemia
E adrenocortical insufficiency
C
Acquired hypothyroidism is the most common disturbance of thyroid function in childhood. Most cases of acquired hypothyroidism in children are the result of autoimmune thyroid disease.
The most common manifestation is a decrease in growth rate resulting in short stature.
If hypothyroidism occurs in adolescence, it is also associated with delayed puberty.
Another common presentation is altered school performance.
Other common symptoms are sluggishness, lethargy, cold intolerance, constipation, dry skin, brittle hair, facial puffiness and muscle aches and pains.
On physical examination, findings include short stature and increased weight for height.
A goitre may or may not be present.
Children with long-standing hypothyroidism have puffy myxoedematous facies.
Cardiovascular examination may show bradycardia, low systolic blood pressure, and muffled heart tones if a pericardial effusion is present.
On neurologic examination, deep tendon reflexes tend to have a delayed return phase.
A minority of children may actually present with pseudoprecocious puberty.
Rickets results from a deficiency of vitamin D. This condition predominantly affects the long bones and skull.
Vitamin C deficiency results in scurvy, a condition with impaired collagen formation. The clinical manifestations may include changes in the gums, loosening of teeth, brittle bones and swollen joints.
Pallor is the most important sign of iron-deficiency anaemia. Children may also have the desire to ingest unusual substances such as ice or dirt.
Finally, hyponatraemia and hypoglycaemia are the prominent presenting signs of adrenal insufficiency in infants.
SPSE 1
A 10-year-old boy has recently been diagnosed with sporadic hyperparathyroidism (HPT). Compared with MEN1 associated HPT, this patient’s disease is most likely to involve:
A a single parathyroid gland
B all four parathyroid glands
C the thyroid gland
D the pituitary gland
E none of the above.
A
Sporadic primary hyperparathyroidism (HPT) is genetically distinct from its MEN-associated disease.
Whereas MEN-associated disease tends to produce diffuse multiglandular parathyroid involvement, sporadic primary HPT tends to involve only a single gland.
The difference in number of glands involved in sporadic vs. MEN-associated disease has important implications for surgical management of patients with primary HPT.
In MEN-associated HPT, most surgeons advocate exploration with identification of all four glands.
The specifics of which procedure to perform in MEN-associated disease, however, are controversial.
Some surgeons advocate total parathyroidectomy with autotransplantation while others prefer subtotal or 3½ gland parathyroidectomy.
In contrast, surgical therapy for sporadic adenomas may be directed at removal of the single adenomatous gland – especially with the use of localisation imaging and intraoperative parathyroid hormone testing.
SPSE 1
A 16-year-old female presents with a 4 cm nodule of the lower pole of the left lobe of the thyroid gland. It is mildly tender and there are no palpable lymph nodes. Her TSH level is low. She is referred to you with an ultrasonography scan (see Figure 72.1a) and nuclear scan (see Figure 72.1b). What is the next step in management?
A total thyroidectomy
B left lobectomy
C thyroid antibody studies
D FNA of the nodule
E CT of the neck
D
Although thyroid nodules are uncommon in children, their importance stems from a relatively high likelihood of associated cancer.
In more recent paediatric studies, the incidence of malignancy in thyroid nodules has been 20% or less. This is a much lower incidence of cancer than was reported in previous decades and is believed to reflect the decreased number of children who have been exposed to neck radiation for trivial reasons.
In a child with a palpable solitary nodule, measurement of free T4, TSH and thyroid antibodies (antithyroglobulin and antithyroid peroxidase) is generally carried out to evaluate thyroid function and screen for autoimmune thyroiditis.
When evaluating a sporadic thyroid nodule in a symptomatic paediatric patient, it is critical to determine whether the nodule is malignant or benign.
The most important diagnostic test at this point is FNA. The technique is easily accomplished in nodules larger than 1 cm in diameter; smaller lesions may require ultrasound guidance.
Interpretations are classified as benign tumour, malignant tumour, indeterminate diagnosis or inadequate specimen.
In children, the effectiveness of FNA cytology in the evaluation of thyroid nodules is still being debated.
Children are somewhat more difficult to evaluate than adults, owing to the smaller size of the nodules, and the frequent need to sedate the child to allow safe and accurate aspiration.
Also, there is a higher incidence of cancer in any thyroid nodule in young children.
It is widely accepted to use FNA in adolescent patients because the pattern of thyroid disease is similar to that of adults.
CT scan will not reliably separate benign from malignant nodules Total thyroidectomy is not indicated at this time.
SPSE 1
An 11-year-old male presents to your clinic complaining of muscle weakness. On exam his BP is 150/90. His serum potassium level is 2.9. He underwent a CT scan of his abdomen (see Figures 72.2a and 72.2b) what’s the diagnosis?
A Cushing’s syndrome
B phaeochromocytoma
C adrenal hyperplasia
D adrenal adenoma
E neuroblastoma
D
Signs and symptoms of primary hyperaldosteronism are non-specific.
Children usually present with hypertension, muscle weakness, polydipsia and polyuria.
Constant high levels of aldosterone causes the total body sodium level to increase, thus increasing the total fluid volume and suppressing renin and angiotensin.
When a child presents with hypertension and hypokalaemia, one should consider a diagnosis of primary hyperaldosteronism.
once the diagnosis is confirmed, it is necessary to determine whether it is due to an adenoma or to bilateral adrenal hyperplasia.
If a mass greater than 1 cm is identified by CT scan or mRI, adenoma is likely.
If no masses are visualised, a selective adrenal vein sampling can differentiate unilateral vs. bilateral adrenocortical hypersecretion.
SPSE 1
An 11-year-old male presents to your clinic complaining of muscle weakness. On exam his BP is 150/90. His serum potassium level is 2.9. He underwent a CT scan of his abdomen (see Figures 72.2a and 72.2b) .
What is the next step in management of the patient?
A percutaneous biopsy
B radiation
C bilateral adrenalectomy
D unilateral adrenalectomy
E spironolactone
D
In patients with adrenal hypercortisolism of unilateral adrenal origin, the treatment is operative removal of the gland.
Perioperative exogenous glucocorticoid replacement is required because the contralateral gland is suppressed.
The surgical approach to the adrenal gland depends on the size of the lesion, the likelihood of malignant disease, the need for bilateral adrenalectomies, and the surgeon’s preference.
If adrenocortical carcinoma is suspected, then an open transabdominal approach is necessary to widely excise the tumour and to thoroughly search for metastatic lesions.
laparoscopic adrenalectomy has emerged as the standard treatment for most patients, including paediatric, when malignancy is not suspected.
laparoscopic approaches can be lateral transabdominal or retroperitoneal.
SPSE 1
