Genetic disorders of the endocrine system

What is this?

typically see increased TSH, low T4, and pts can have enlarged thyroid (goiter) if untreated

congenital hypothyroidism

what is this?

high TSH and low free T4 VS low/normal TSH and low T4

high TSH: primary congenital hypothyroidism

low TSH: secondary/central hypothyroidism (the thyroid isn’t the problem)

if treating hypothyroidism with thyroid hormone, what aspects can get to normal and what cant?

bone age and height can increase to normal but mental age may not; this is why early detection is important

what is this?

common symptoms of polyuria, polydipsia, and chronic dehydration

diabetes insipidus (central or nephrogenic)

what is this?

decrease in the release of ADH VS a decrease in the response to ADH

release: central diabetes insipidus

response: nephrogenic diabetes insipidus

explain how we determine central vs nephrogenic diabetes insipidus and what the results are

water deprivation or desmopressin test:

central = decreased vasopressin made so if we give desmopressin then this will help

nephrogenic = decreased response to vasopressin, so giving desmopressin won’t fix/help anything

what is this?

mutations in ADH gene

central diabetes insipidus

what is this?

mutations in AVPR2 or AQP2

nephrogenic diabetes insipidus

what is this?

21-hydroxylase deficiency and mutation in CYP21A2 gene

congenital adrenal hyperplasia

What is this?

ambiguous genitalia, early virilization, salt wasting

congenital adrenal hyperplasia

what is a non-genetic perinatal stress leading to hyperinsulinism?

preeclampsia

What is this?

mutations in insulin secretion

congenital hyperinsulinism

what is this?

most common mutations are in the Katp channel

congenital hyperinsulinism

what is this?

insulin secretion constant “on” signal without regulation by glucose

congenital hyperinsulinism

what is this?

biallelic recessive mutations; all pancreatic beta-cells affected

diffuse hyperinsulinism

what is this?

“2 hit hypothesis”; inherited paternal mutation and somatic maternal loss of allele

focal hyperinsulinism (loss mom and dad changes)

what is this?

results in hypoglycemia

congenital hyperinsulinism

_____ hyperinsulinism presents earlier. what do we see?

diffuse; babies on average are heavier and larger in size (remember insulin can act as a growth factor)

which hyperinsulinism type has higher insulin levels (both of them have increased levels)

diffuse more than focal

what is this?

2/3 of the main endocrine tumors: parathyroid, enteropancreatic, and pituitary

MEN type 1

what is this?

primary hyperparathyroidism is usually the first clinical sign

MEN type 1

what are 3 main contributors to short stature?

dependent on uterine growth conditions, environment during childhood, and genetics

what is it important to do with females with short stature?

karyotype to rule out turner even without signs of classical presentation

with growth failure, explain seeing only postnatal growth restriction, vs uterine and postnatal growth restriction

normal at birth then not: GH issue (this is because GH only acts postnatally)

growth restricted even in the womb: IGF-1 function issue (this is because IGF-1 functions pre and postnatally)

what is this?

GHT mutations, normal birth size/weight, midface hypoplasia, intellect and head development normal, and low IGF-1 in serum

Laron syndrome

what is this?

no GH in serum, GH1 mutation, severe VS some GH response, mutation in GH1 or GHRHR, mild

no GH: IGHD type 1a

some GH: IGHD type 1b