Endocrinology Flashcards
A four-year-old girl presents with precocious puberty. Her parents first noticed breast bud development five months ago. She has since progressed to Tanner stage III breast development and stage II pubic hair. Investigations demonstrate
LH 1.5 (RR 0.02-0.3 for age), FSH 5.0 (RR 0.5-4.5), 17-beta-oestradiol 30pmol/L (RR <10 for age).
MRI brain shows a mass.
Elevated LH and FSH is suggestive of central precocious puberty. CPP in girls is only pathological in 10-20% of cases, but is more likely to be pathological if onset is at <6 years of age and/or is rapidly progressive. Hypothalamic hamartomas are the most common CNS cause of precocious puberty; in some cases puberty is preceded by gelastic seizures. Puberty in these instances is always isosexual. In NF1, optic gliomas interrupting the HPG axis are the most common cause of CPP. Regardless of the causative lesion, treatment with a GnRH-agonist is the treatment of choice for halting pubertal development.
A 16-year-old boy is referred to you due to delayed puberty. On questioning he also reports anosmia. O/E he has Tanner Stage I development with 3mL testes and stretched penile length of 6cm. His investigations demonstrate pre-pubertal levels of LH, FSH, and testosterone.
Kallmann syndrome is an inherited disorder which causes hypogonadotropic hypogonadism and hyposmia/anosmia. Neurons which migrate from the olfactory placode to the hypothalamus are impaired, resulting in inability to produce sufficient GnRH to stimulate pubertal development. Other features may include micropenis, undescended testes, midline facial defects, and congenital solitary kidney. Hormone replacement is the mainstay of treatment.
A thre-year-old girl presents with bilateral breast development. She is previously well. To examine her height and weight are on the 75th centile. You note facial asymmetry, with prominence of the left periorbital area. There is no proptosis or opthalmoplegia. She has four small café au lait macules with irregular borders on her posterior torso. She has Tanner stage II breast development and stage I pubic hair. Her skull xray shows fibrous dysplasia.
McCune-Albright syndrome is syndrome caused by a somatic mutation in the G-protein that stimulates cyclic-AMP. It thus causes a variable expression depending on which tissues are affected. It is characterised by fibrous dysplasias of bone, café au lait macules with an irregular ‘coast of Maine’ border (which may occur on one side of the body), and endocrinopathies. The most common endocrine presentation is peripheral precious puberty, which is more common in girls than boys due to ovarian cyst formation with autonomous estrogen production. In later life, central precocious puberty tends to override the initial peripheral precocity. Pituitary, thyroid and adrenal manifestations may also occur. Aromatase inhibitors or anti-oestrogen medications may be used to limit oestrogen effects on pubertal and bone development, but have variable success.
MODY: Maturity Onset Diabetes of Youth
All subtypes of MODY are monogenic defects of beta-cell function with autosomal dominant inheritance. Classically, onset is before 25 years of age in at least one family member.
MODY3 is the most common type, is due to a mutation in HNF1a, and patients are typically very responsive to treatment with sulfonylureas. MODY2 is due to a mutation in Glucokinase, and typically has a benign course not requiring treatment. Genetic testing by Sanger Sequencing/NextGen Sequencing allows diagnosis of any point mutations in the relevant genes.
DKA is rare
Patients with MODY are classically non-obese patients, who otherwise tend to have similar clinical features to those with Type 2 diabetes without clinical features of insulin resistance.
Acanthosis nigricans NOT typically found in MODY
short stature investigations
Short stature is defined as height <3rd centile for age. Only around 5% of cases are pathological. Initial evaluation should consist of history, examination, and calculation of growth velocity, BMI, and mid-parental height. Bone age x-ray can help to narrow down the differential diagnosis.
Normal variants of growth include familial short stature, constitutional growth delay, and IUGR with catch up growth. If your initial evaluation is consistent with one of these conditions, then investigation may not be required.
Of pathological causes, the most common causes are Coeliac disease, Growth Hormone deficiency, hypothyroidism, and Turner syndrome. Other systemic diseases, genetic conditions, and endocrine abnormalities should also be considered
Karyotype is indicated in girls to assess for Turner syndrome. Genetic testing is not a first line investigation in boys unless there are dysmorphic features or other signs of a genetic disease (such as achondroplasia, Noonan’s syndrome, William’s syndrome, Silver-Russel syndrome, or SHOX gene mutation). Depending on which condition you suspect, genetic testing for these conditions may involve CGH array, FISH, or ‘NextGen’ Sequencing for SNPs. Karyotype is recommended in girls with short stature as this may be the only feature of Turner’s syndrome before pubertal delay becomes evident later in life.
IGF-1 is produced in the liver, is the primary mediator of the effects of growth hormone, and can be measured at any time of day without the need for stimulation testing.It has approximately an 80% sensitivity for the detection of GH deficiency. It is useful in the investigation of pathological short stature. However, GH stimulation testing remains the gold standard.
TSH and free T4 should be tested in all patients where pathological short stature is suspected.
Anti-TTG and total IgA should be used to investigate for Coeliac disease as a cause of short stature. Classically these patients will have normal growth until the introduction of solids at 6 months of age. Coeliac disease may develop at any point after the introduction of gluten to the diet. Associated symptoms of abdominal pain, loose stools, constipation, bloating, and poor weight gain may also be noted.
