Endocrine

A 14-year-old girl arrives as a new patient. She was followed for 7 years in another state with a history of insulin-dependent dia¬betes mellitus. Her hemoglobin Alc is 14.9%. This laboratory test indicates that:
A. She does not have insulin-dependent diabetes.
B. She has an underlying infection.
C. Her glucose control is poor.
D. She is demonstrating the Somogyi phenomenon.
E. She has entered the “honeymoon phase” of her diabetes.

C. The patient in the question likely has poor diabetes control. The hemoglobin AIC is a test commonly used to follow glucose control. It measures the average glucose levels the patient has ex­perienced over the previous 2 or 3 months. The goal for hemo­globin AIC for most diabetics is usually 6% to 7.5% Hemoglobin AIC. The Somogyi phenome­non refers to a patient who has hypoglycemic episodes at night manifested as night terrors, headaches, or early morning sweat­ing who present a few hours later with hyperglycemia, ketonuria, and glucosuria; an outpouring of counter-regulatory hormones in response to the hypoglycemia is responsible for the hyper­glycemic episode.

Six months after being diagnosed with what appears to be insulin-dependent diabetes, a 5-year-old child demonstrates a significant decrease in his requirement for insulin. The explanation for this is most likely?
A. His diagnosis of insulin-dependent diabetes was wrong.
B. He had a chronic infection that is now under control.
C. He has followed his diabetes diet so well that he needs less insulin.
D. He is demonstrating the Somogyi phenomenon.
E. He has entered the “honeymoon phase” of his diabetes.

A large number of newly diagnosed diabetic patients (up to 75%) have a progressive drop in the daily requirement of insulin in the months following their initial diagnosis of diabetes; a few patients require no insulin. This “honeymoon” period usually lasts a few months, but most often a requirement for insulin returns. Patients should be counseled that the “honeymoon” period is not a cure, and that they almost certainly will require insulin again.

A 16-year-old obese girl presents-with enuresis, frequent urina¬tion, a white vaginal discharge, and a dark rash around her neck. Her serum glucose is 250 mg/dL, and her urinalysis is positive for 2 + glucose, but is otherwise negative. She most likely has:
A. Chlamydia cervicitis
B. Urinary tract infection
C. Psoriasis
D. Chemical vaginitis
E. Type II diabetes

E. The description is of an obese child with candida vaginitis (causing the vaginal discharge) and acanthosis nigricans (the dark rash around the neck) consistent with type II diabetes. This condition is far more common in overweight children, especially those with a family history of the condition.

A father brings in his 4-year-old son who has started pubic hair. The child has also recently exhibited “bullying” behavior at his preschool. History reveals that the child was a full-term infant who had no postnatal complications. The child takes no medications. Family history is unremarkable. He has one younger sister who is well. Physical exam reveals a white male who is above the 95th percentile for weight and height, with marked muscular development, Tanner stage II pu¬bic hair development, scanty axillary hair, prepubertal testicular size (2.5 cm), a voice with a masculine quality, and skin with oiliness. The abdominal examination is normal. The child’s bone age is 6 years old. The next step in the care of this child is:
A. Magnetic resonance imaging (MRI) of the brain.
B. Serum 17 α-hydroxyprogesterone level.
C. Ultrasonogram of the testes.
D. Reassurance to the family.
E. Dexamethasone challenge test

B. Boys with congenital adrenal hyperplasia have virilization despite prepubertal testicles. The virilization results from a disorder of steroid synthesis, leading to a deficiency of cortisol and overproduction of androgenic intermediary metabolites such as 17a-hydroxyprogesterone.

A mother brings in her 14-year-old son into clinic because his teacher has expressed repeated concerns about his poor school performance and maladjusted behavior. He has poor grades in math, spelling, and reading. The boy is extremely shy and has always had difficulty in adjusting socially. Physical examination reveals a slim boy at the 95th percentile for height and the 5th percentile for weight on standardized growth curves: It is very difficult to engage him in conversation. The testes are prepu¬bertal (<2.5 cm) and he has mild hypospadias. He has no secondary sexual characteristics. Which of the following is most likely cause of this boy’s delay in puberty?
A. Testicular tumor
B. Hypopituitarism
C. Noonan syndrome
D. Klinefelter syndrome
E. Marfan syndrome

D. Klinefelter syndrome (47,XXY) usually comes to growth attention because of gynecomastia and small testes. These male infants are usually clinically normal at birth. Treatment involves placement therapy with a long-acting testosterone beginning at the age 11 to 12 years.

A mother brings in her l-week-old son who has vomited four times over the last 24 hours. He has no fever or diarrhea and no one in the home has been ill. The infant is breast-feeding poorly and appears to be “floppy” to the mother. He has had only one wet diaper in the last 12 hours. The physical examination reveals a lethargic ill-appearing infant who has lost 250 g since birth; his pulse is 110 beats per minute; his buccal mucosa is dry, and he lacks skin turgor. In addition to stabilization procedures and measurement of his serum electrolytes, what endocrinologic test would be reasonable to consider?
A. Serum cortisol level
B. Urine cortisol level
C. Serum 21-hydroxylase level
D. Serum 17 α -hydroxyprogesterone level
E. Serum testosterone level

D. Male infants with salt-losing congenital adrenal hyperplasia develop clinical symptoms that are easily confused with those of pyloric stenosis, intestinal obstruction, heart disease, cow’s intolerance, or other causes of failure to thrive. Their genitalia appear normal. A serum l7a-hydroxyprogesterone level, would be elevated in this infant. Without appropriate treatment (hydrocortisone, mineralocorticoid and sodium supplementation) cardiovascular collapse and death may occur within a few weeks. Many states have neonatal screening programs for CAH) yet in infants with salt-losing CAH (2 I-hydroxylase deficiency) can become very ill and die before the screening results are known.

A mother brings in her 15-year-old daughter because she has never started her periods. She otherwise is healthy and takes no medications. Her past medical history is unremarkable except for inguinal hernia repair as an infant. Family history is unre¬markable. Physical examination reveals a white female who is at the 75th percentile for height and weight. She has Tanner stage IV breast development and no pubic or axillary hair develop¬ment. Her anogenital examination reveals a short pocket-like vaginal opening. Which of the following is the most likely ex¬planation for the child’s amenorrhea?
A. Congenital adrenal hyperplasia
B. Turner syndrome
C. Testicular feminization
D. Pituitary tumor
E. Adrenal tumor

C. Testicular feminization is a result of decreased androgen binding to target tissues or androgen insensitivity. These individuals have 46XY karyotypes yet appear as phenotypically normal females with a short or atretic vagina. Maintaining female gender assignment is appropriate; and vaginoplasty is frequently needed after puberty.

You examine a full-term 3780-g newborn in the nursery and notice that he has marked hypotonia, a very small penis, and unilateral cryptorchidism. Which of the following is the most explanation for this infant’s findings?
A. Maternal treatment with steroids
B. Congenital adrenal hyperplasia
C. Mixed gonadal dysgenesis
D. Male disorder of sex development.
E. Prader- Willi syndrome

E. Although severe hypotonia, failure to thrive and hypogonadism characterize Prader Willi syndrome in early life, hyperphagia, obesity, mental retardation and bizarre behavior become manifest by age 6 years. The insatiable appetite leads in many cases to morbid obesity, limited sexual function, and sever behavioral abnormalities. Mixed gonadal dysgenesis a reasonable choice because of the unilateral cryptorchidism and hypogoandism, yet unlike infants with Prader-Willi syndrome, these infants do not exhibit severe hypotonia.

An 8-year-old boy is evaluated for short stature. His mother re¬ports that he has begun to gain quite a bit of weight over the last year, that he has little or no energy, he sleeps more than normal, and he complains of being cold all the time. His growth curve demonstrates that he has fallen from the 50th percentile for height to the 5th percentile for height, but his weight has in¬creased to the 90th percentile for height. On physical examina¬tion he is obese, has immature facies, thin hair, and slow re¬flexes. The most appropriate course of action for this child is to:
A. Order Epstein-Barr virus titer
B. Measure thyroid function
C. Reassure the mother that the child has normal prepubertal development
D. Determine bone age
E. Order a somatomedin C level

B. This child has classic symptoms of acquired hypothyroidism. A bone age would be delayed, but the tests necessary to diag­nose his condition are thyroid function studies. Thyroid hor­mone replacement therapy should resolve these symptoms and growth should resume normally.

A mother brings her 4-year-old girl to your clinic. The girl has bilateral breast development that was first noticed 6 months ago the child takes no medications and there is no source of exogenous estrogen in the home. The family history is unremarkable. The physical exam reveals a female who is 50th percentile for height and weight, has normal blood pressure, normal skin, Tanner stage II breasts, soft abdomen without palpable masses, no body odor, neither pubic nor axillary hair, Mild estrogenization of the vagina. Which of the following is most likely explanation for the child’s breast development?
A. Central precocious puberty
B. Premature thelarche
C. Congenital adrenal hyperplasia
D. An adrenal tumor
E. Premature adrenarche

B. All of this child’s findings are estrogen related. She has no virilization. Postulated causes of premature thelarche include ovarian cysts and transient gonadotropin secretion. No management is necessary.

A child aged 10 days has ambiguous genitalia. Which of the following is correct statement
a. if a buccal smear is chromatin negative there is a serious risk of an Addisonian crisis
b. a raised urinary output of pregnanetriol would confirm a diagnosis of congenital adrenal hyperplasia
c. the finding of the genotype 45 XO would reliably explain the anomaly
d. if testicles are present in the “labia” an acceptable explanation would be Klinefelter’s syndrome
e. the most important factor in deciding the sex to which the child should be assigned is the genetic (chromosomal) sex

Comments: answer is b

If the buccal smear positive ie female then there would be at increased risk of salt crisis. Salt losers presenting in newborn period with crisis are more likely to be female. The commonest cause of ambiguous genitalia at birth is CAH, of which 95% are deficient in 21-hydroxylase.

Less common enzyme defects involve 11B hydroxylase, and 3B hydroxysteroid dehydrogenase. About 2/3 of 21-hydroxylase are salt losers, and present with an hypoadrenal crisis.

There is normal genitalia in 47 XXY – Klinefelter’s and Turner’s – XO. In disorder of sex development states, the assignation of sex is not totally based on the karyotype.

2 week old male child is brought to casualty by his concerned parents with diarrhoea and
vomiting. He is the first child of a young couple. Examination reveals few features besides
obvious dehydration. He is noted to have a penile length of 3.5cms. Which of the following is
the most appropriate initial treatment for this patient?
a. Cow’s milk allergy is the most likely diagnosis
b. gluten-enteropathy should be excluded
c. Requires urgent treatment with oral steroids
d. Requires urgent treatment with IV normal saline
e. Rota virus gastroenteritis is the most likely diagnosis

Comments:the answer is d

The history suggests a diagnosis of classical congenital adrenal hyperplasia which is commonly due to 21 hydroxylase deficiency. A variable presentation is typical but neonatal presentations include salt losing crisis, penile development in the male virilisation and ambiguous genitialia in females.

Patients should initially be resuscitated with fluid, usually saline and if suspicious, urgent biochemistry requested for cortisol, 17OHP etc prior to administration of intravenous steroids.

A 16 year old female presents with hypertension and increasing weight. Which of the following features would be most suggestive of Cushing’s syndrome rather than simple obesity?
a. Abdominal striae
b. Acanthosis Nigricans
c. Buffalo Hump (interscapular fat pad)
d. Moon face
e. Proximal myopathy

Comments: the answer is e

Proximal myopathy, easy bruising and thin skin are clinical features that are most suggestive of Cushing’s syndrome. Otherwise, abdominal striae, buffalo hump, and acanthosis nigricans are all features of obesity.

Similarly Oligomennorhoea would be a feature of obesity/polycystic ovarian syndrome.

Which of the following statements applies to precocious puberty:
a. Is less common in girls
b. In boys it is usually idiopathic
c. Is a well recognised sequel to hydrocephalus
d. Is associated with a normal rate of skeletal maturation
e. Is treated with LHRH antagonists.

Comments:the answer is c

Precocious puberty is approximately five times more common in females. In females it is usually idiopathic, in males the commonest cause is a hypothalamic hamartoma. CNS disorders such as hydrocephalus, head trauma, cerebral palsy and meningitis are aetiological factors.

Which of the following techniques would be most useful in the differential diagnosis between ectopic Cushing’s syndrome and pituitary dependent Cushing’s disease.
a. Urine free cortisol
b. High dose Dexamethasone suppression test
c. ACTH concentrations
d. Inferior petrosal sinus sampling
e. CRF test

Comments: the answer is d

Inferior petrosal sinus sampling with an elevated central ACTH concentration compared with the peripheral value is the most valuable test in the differential diagnosis of either Cushing’s disease or ectopic Cushing’s syndrome. The other tests are far less useful in comparison.

Causes of hypoadrenalism include:
a. Hughes’ syndrome (anti-phospholipid antibody)
b. MEN type 2a
c. VonHippel-Lindau
d. Pendred’s syndrome
e. McArdle’s syndrome

Comments: the answer is a

The anti-phospholipid syndrome is one of the commoner causes of Hypoadrenalism and may precipitate adrenal infarction and haemorrhage through adrenal vein thrombosis.

Carcinoid tumours of the foregut may be associated with which of the following
a. Cushing’s syndrome
b. Hypercalcaemia
c. Pellagra
d. Pulmonary hypertension
e. Carcinoid syndrome

Comments: answer is a

Carcinoid tumours of the foregut unlike tumours of the midgut are not associated with carcinoid syndrome but may secrete CRF/ACTH resulting in ectopic Cushing’s syndrome.

Other associated conditions include somatostatinoma, Zollinger-Ellison syndrome and Acromegaly (ectopic GHRH).

Which of the following is true of IGF-1 concentrations
a. Concentrations are reduced in pregnancy
b. Concentrations are elevated in hepatic cirrhosis
c. Concentrations are usually elevated in adult growth hormone deficiency
d. Concentrations are reduced in starvation
e. Concentrations are elevated in diabetes mellitus

Comments: answer is d

IGF-1 concentrations are often increased in pregnancy. Reduced IGF-1 is typically found in adult GHD, Cirrhosis of the liver due to reduced synthesis, diabetes mellitus and starvation.

A 16 year old female with Addison’s disease is intolerant of her hydrocortisone treatment
which she takes at a dose of 20mg in the morning and 10mg in the evening. Which of the
following doses of prednisolone would provide an equivalent daily dose as her hydrocortisone?
a. 15mg
b. 7.5mg
c. 10mg
d. 12.5mg
e. 15mg

Comments: answer is b

The equivalent ratio of prednisolone to hydrocortisone is 4:1.

For Dexamethasone to hydrocortisone the ratio is roughly 40:1

A 18 year-old girl presents with anxiety and palpitations. Her mother had been treated for an overactive thyroid gland having received radioiodine and was now on Thyroxine replacement therapy, she found few tablets missing. On examination she had a pulse of 104 bpm with a fine tremor and lid lag. There was no goitre palpable. Investigations revealed:
serum free T4 33 pmol/L (10-20)
plasma thyroid stimulating hormone (TSH) <0.05 (0.5-4.5)
serum antithyroid peroxidase (anti TPO) titre 40 IU/L (<50)
What is the most likely cause of her symptoms?

a. factitious thyrotoxicosis
b. familial hyperthyroglobulinaemia
c. Hashitoxicosis
d. Graves’ disease
e. Riedel’s thyroiditis

Comments: the answer is d

Although the lead-in might make you think that this patient could gain access to thyroxine and so a diagnosis of factitious hyperthyroidism is possible, in practice this is extremely unlikely.

A strong family history of thyrotoxicosis is typical for Graves’ disease and the absence of a goitre with the absence of TPO antibodies (found in 80% of Graves cases) again is compatible with a diagnosis of Graves.

A patient is receiving treatment with recombinant human growth hormone. Which of the
following is a recognised side effect of GH therapy?

a. Prostatic hypertrophy
b. Melanoma
c. Benign intra-cranial hypertension
d. Prolongation of the QT interval
e. Osteoporosis

Comments: the answer is c

GH is rarely associated with BIH, the mechanism probably is related to fluid retention.

The commonest side effect of GH therapy is fluid retention, though other side effects include gynaecomastia, hypertension and atrial fibrillation. BPH has not been reported.

Longitudinal growth:
A Is relatively more affected than weight gain in hypothyroidism.
B Is severely retarded in growth hormone deficiency in the first year of life.
C Is more dependent on maternal than paternal height.
D Is greater in the mid trimester of pregnancy than in any period in postnatal life.
E Is irreversibly damaged in intrauterine malnutrition

Answer is a

Effect of growth hormone deficiency usually appear after the first year of life. Longitudinal growth depends on both maternal and paternal height and is maximum during the third trimester. Infants with intrauterine malnutrition can catch up and retain normal height.

The causes of true precocious puberty in a 7-year-old may include:
A Hypothyroidism
B Congenital adrenal hyperplasia
C Craniopharyngioma
D McCune-Albright Syndrome
E Fragile X Syndrome

Answer is a

Congenital adrenal hyperplasia and McCune-Albright Syndrome are associated with pseudoprecocious puberty. Craniopharyngioma usually causes delayed puberty rather than precocious one (though there is case reports of precocious puberty associated with craniopharyngioma it is extremely rare). Fragile X Syndrome usually have puberty at normal time in spite of macro orchidism.