Endocrine Flashcards
Definition and causes of micropenis
Micropenis is defined as a normally formed penis that is at least 2.5 standard deviations below the mean in size. Stretched penile length of the newborn is typically 3.5cm (+/- 0.7), diagnosis is made on a length of <1.9cm. Micropenis results from a hormonal abnormality that occurs after 14wks of gestation, commonly:
1) Hypogonadothropic gonadism = secondary hypogonadism (most commonly GRH deficiency e.g. Kallmann synd, Prader Willi or Lawrence Moon-Biedl)
2) Hypergonadotrophic gonadism (primary testicular failure)
3) Idiopathic micropenis
Congenitalpanhypopituitarism is characterised by:
1) Micropenis – FSH/LH def – usually small but normal appearing penis, small testes
2) Optic atrophy
3) Midline defects
4) Poor growth
5) Hypoglycaemia – due to severe GH and/or ACTH def – jitteriness, irritability, seizures
Presentation depends on severity of deficiency. Some come to attention because of low thyroid levels on Guthrie screen, others may present with hypernatraemic diabetes insipidus, and older children most commonly present with growth failure at any age.
Presentation of classic CAH
Commonest is 21-hydroxylase deficiency, ‘classic’ CAH, 50% of these have salt wasting form. Usually presents with an adrenal crisis at 2-3 weeks of age (FTT, vomiting, hypotension, dehydration, hyponatraemia, hyperkalemia, hypoglycaemia, shock).
Females have ambiguous genitalia at birth due to virilizing effects of excess androgens inutero
Males not identified early in neonatal period because normal genitalia
5 alpha-reductase deficiency
Autosomal recessive ‘intersex’ condition -5AR converts testosterone to the more physiologically active dihydrotestosterone (DHT). DHT is required for masculinisation of male external genitalia in-utero. Genotypicaly male, phenotypically variable – from mildly undervirilised male genitalia with isolated micropenis or hypospadias to marked undervirilisation with female genitalia with clitoral enlargement. Have internal testes, wolffian organs. No uterus, fallopian tubes, may have pseuodovagina. May be misdiagnosed for androgen insensitivity syndrome, until puberty when start to virilise instead of feminise
primary amenorrhoea, sterility, short 4th metatarsal, wide spaced nipple, webbed neck, short stature, lack of development of primary and secondary sexual characteristics, pigmented naevi, increased urinary gonadotrophins.
Turner syndrome – a gonadal dysgenesis syndrome.Female phenotype -45X (also written as 45XO) is commonest genotype. Mosaicism is 45X/46XY – a non-dysjunction event in the zygote creates a cell line that is missing an X. If happens early -Turner syndrome; if happens late - normal male.
Signs - primary amenorrhoea, sterility, short 4th metatarsal, wide spaced nipple, webbed neck, short stature, lack of development of primary and secondary sexual characteristics, pigmented naevi, increased urinary gonadotrophins.
Action of 1,25-dihydroxycholecalciferol to increase plasma Ca
Promotes activation of osteocalcin and alkaline phosphatase production by osteoblasts, and the differentiation of osteoclasts precursors, having a net effect in mobilising calcium and phosphate from bone.
In the kidney, 1,25-dihydroxycholecalciferol facilitates the action of PTH on distal tubule calcium absorption.
The growth promoting effects of Growth Hormone (GH) are mostly mediated by?
Specific effects of GH
GH acts by binding to a specific receptor, located mostly in the liver, and inducing intracellular signaling by a phosphorylation cascade. Its predominant action is to stimulate hepatic synthesis and secretion of IGF-I, a potent growth and differentiation factor.
As a differentiating and growth factor, IGF-I is a critical protein induced by GH, and is likely responsible for most of the growth-promoting activities of GH.
Furthermore, IGF-I also directly inhibits GH secretion and GH receptor function by a negative feedback loop.
Specific effects
GH stimulates linear growth in children by acting directly and indirectly (via the synthesis of IGF-I) on the epiphyseal plates of long bones.
GH also has specific metabolic actions including:
Increased lipolysis and lipid oxidation, which leads to mobilization of stored triglyceride
Stimulation of protein synthesis
Antagonism of insulin action
Phosphate, water, and sodium retention
Insulin requirements in diabetes
Pre/Mid/end puberty
Pre-pubertal children require about 0.7U/kg/day
1U/kg/day mid puberty
1.2U/kg/day by end of puberty.
Mechanism of thiazolidinediones
The thiazolidinediones, also known as glitazones, are a class of medications used in the treatment of Type 2 diabetes mellitus. They were introduced in the late 1990s.
They increase insulin sensitivity by acting on adipose, muscle, and liver to increase glucose utilisation and decrease glucose production.
The mechanism by which the thiazolidinediones exert their effect is not fully understood. They bind to and activate one or more peroxisome proliferator-activated receptors, which regulate gene expression in response to ligand binding.
Rosiglitazone and pioglitazone are registered for use in monotherapy, and in combination with sulfonylureas and metformin. Pioglitazone is also licensed for use in combination with insulin.
Central precocious puberty
Bloods
When is it pathological
Most common causes
Rx
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.
Most common cause of death in DKA
60% mortality due to cerebral oedema
0.3 to 0.9 percent of cases of diabetic ketoacidosis (DKA)
Among children with DKA who develop cerebral injury, the mortality rate is 20 to 25 percent, and 21 to 26 percent of survivors have permanent neurologic sequelae.
What is leptin
Leptin is a 16 kDA protein hormonethat plays a key role in regulating energy intake and energy expenditure (appetite and metabolism).Leptin is released by fat cells in amounts mirroring overall body fat stores. Thus, circulating leptin levels give the brain a reading of energy storage for the purposes of regulating appetite and metabolism.
most commonly deficient hormones following craniopharyngioma surgery.
Vasopressin, also known as ADH
The second most common is growth hormone.
5a-reductase deficiency
Deficiency in which hormone
5a-Reductase is an enzyme required for the conversion of testosterone to dihydrotestosterone, a potent androgen particularly important in the fetal development of male external genitalia. 5a-reductase deficiency thus results in an increased ratio of testosterone: DHT, and ambiguous genitalia in XY individuals. Testosterone production at puberty results in male secondary sex characteristics.
GH in hypoglycemia
Hypoglycaemia usually stimulates GH release as part of the physiological counter-regulatory response. GH and cortisol both increase lipolysis and gluconeogenesis and inhibit the effects of insulin. Severe GH deficiency may cause hypoglycaemia, particularly if it occurs in conjunction with panhypopituitarism. It is thus investigated routinely in the setting of severe, unexplained hypoglycaemia.
