DSA11 - Delayed Puberty, Precocious Puberty, and Galactorrhea

Cortisol

Although Estrogen and Testosterone BOTH provide negative feedback on the HPG axis, which of the 3 HPA hormones is the ONLY hormone to provide negative feedback?

Precocious (FEMALE)

Is this Precocious, Normal, or Delayed puberty in FEMALES?

> Thelarche/Hair (Pubic & Axillary) < 8 y/o

> Menarche < 10 y/o

Normal (FEMALE)

Is this Precocious, Normal, or Delayed puberty in FEMALES?

> Thelarche/Hair (Pubic & Axillary) = 10 y/o

> Menarche = 12.5 y/o

Delayed (FEMALE)

Is this Precocious, Normal, or Delayed puberty in FEMALES?

> Thelarche/Hair (Pubic & Axillary) > 12 y/o

> Menarche > 15 y/o

Precocious (MALE)

Is this Precocious, Normal, or Delayed puberty in MALES?

> Testicular Enlargement < 9 y/o

> Pubic/Axillary Hair < 10 y/o

Normal (MALE)

Is this Precocious, Normal, or Delayed puberty in MALES?

> Testicular Enlargement = 11.5 y/o

> Pubic/Axillary Hair = 12 y/o

Delayed (MALE)

Is this Precocious, Normal, or Delayed puberty in MALES?

> Testicular Enlargement > 14 y/o

> Pubic/Axillary Hair > 14.5 y/o

Gonadal Injury

Define Condition:

Type of PRIMARY Puberty condition - An insult to the testicles or ovaries, resulting in the gonads being unable to produce testosterone or estrogen

-Hx:

> Vascular Insufficiency

> Chemo

> Radiation

> Autoimmune

> Trauma

-Path:

> Adrenal gland still produce DHEA-S and AS --> Axillary/Pubic hair, Body Odor, Acne still appear

> Characteristics that need Sex Hormones don't appear (M = Deep voice, facial hair, MSK develop; F = Breast develop, menarche)

-Sx/PE:

MEN

> Fatigue

> Low Libido

> Low muscle mass

> Gynecomastia

> Infertility

WOMEN

> Amenorrhea/Oligomenorrhea

> Hot flashes

> Vaginal dryness

-Dx:

Labs

> FSH/LH = HIGH

> Est/Test = LOW

-Tx: Replacement of Testosterone/Estrogen/Progesterone

Turner Syndrome

Define Condition:

Type of PRIMARY Puberty condition - chromosomal disorder in which female is born w/ single X chromosome

-Hx: Affects 1 n 2,000 live female births

-Sx/PE:

> Gonadal dysgenesis = streak gonads (Small amts of connective tissue and paucity of absence of follicles)

> Short Stature

> Cardiac Malformations involving aortic arch (BICUSPID AORTIC VALVE, Coarctation of Aorta)

> Structural renal anomalies

> Low posterior hairline

> Webbed neck

> Shield chest

> Short 4th metacarpal bone

-Dx:

Karyotype = CONFIRM

Labs

> FSH/LH = HIGH

> Estrogen = LOW

-Tx: Estrogen/Progestrone Replacement +/- Growth Hormone

Klinefelter Syndrome (47, XXY)

Define Condition:

Type of PRIMARY Puberty condition - chromosomal abnormality in which a male is born with two X chromosomes and one Y chromosome

-Hx: 1 in 600 males

-Sx/PE:

> Primary Gonadal Insufficiency

> Small Testes

> TALL STATURE

> Eunuchoid Habitus (arms and legs are disproportionately long relative to the torso)

> Gynecomastia

> Learning Disabilities

-Dx:

Karyotype = CONFIRM

Labs

> FSH/LH = HIGH

> Test = Low(ish)

-Tx: Testosterone Replacement

-Prog:

> Infertility

> Breast cancer

> Mediastinal germ cell. tumors

Constitutional delay of growth and puberty ("Late Bloomer")

Define Condition:

Type of SECONDARY Puberty condition - NOT pathologic, but variant of normal

-Hx: FHx of Late Puberty

-Sx/PE: Healthy

-Dx:

Labs

> FSH/LH = LOW

> Test/Est = LOW

Bone Age = DELAYED

-Tx: Reassurance, Testosterone in Boys (jump start)

Kallmann Syndrome

Define Condition:

Type of SECONDARY Puberty condition - genetic condition notable for abnormal migration/development of GnRH-releasing neurons and olfactory neurons

-Sx/PE:

> Delayed/Incomplete/Absent Puberty

> HYPOGONADISM in Adulthood (if UnTx)

> Anosmia (60%)

-Dx:

Molecular Genetic Analysis

Labs

> FSH/LH = LOW

> Test/Est = LOW

MRI = Hypoplasia or Aplasia of Olfactory bulbs/sulci/tracts

-Tx: Replacement of testosterone or estrogen/progesterone

Hypopituitarism

Define Condition:

Type of SECONDARY Puberty condition - diminished hormone secretion from pituitary gland

-Hx:

> Congenital: Mutations

> Acquired:

>> Trauma

>> Radiation

>> CNS Infex

>> Neurosurgical Injury

>> Sellar Tumors

-Path:

-Sx/PE:

-Dx:

Labs

> FSH/LH = LOW

> Test/Est = LOW

MRI (Brain/Pituitary) = Compromised Pituitary gland

-Tx: Replacement of testosterone or estrogen/progesterone + Any other compromised pituitary hormones as well

Sheehan Syndrome

Define Condition:

Type of SECONDARY Puberty condition (Cause of ADULT Hypogonadism) - clinical scenario occurring in response to vascular insufficiency of the pituitary gland that occurs in the early post-partum timeframe

-Path: Pituitary gland enlarged during pregnancy --> more susceptible to vascular insufficiency

-Prog: From Excessive Post-Partum Bleeding

> Hypovolemic Shock

> Inadequate Perfusion of Pituitary Gland

Chronic illness, Undernutrition, Excessive exercise causing "Functional Hypothalamic Hypogonadism)

Define Condition:

Type of SECONDARY Puberty condition - GnRH secretion is diminished, perhaps as a physiologic adaptation, in the setting of illness or an otherwise compromised state of overall health

-Hx:

> YOUNG WOMEN

> High-level of exercise OR Caloric Restriction

-Path: Evolutionary adaptation to prevent pregnancy and conserve energy

-Sx/PE: Amenorrhea (if insult doesn't occur after puberty)

-Dx: DX OF EXCLUSION

Labs

> FSH/LH = LOW

> Test/Est = LOW

Bone Density = Compromised

-Tx: Estrogen replacement

Central Precocious Puberty (CPP)

Define Condition:

When GnRH secretion simply “turns on” ahead of schedule

-Hx:

> Female = IDIOPATHIC (85%)

> Male = Idiopathic (25-60%)

> Non-Idio = CNS LESIONS

>> Hypothalamic Hamartoma (a/w "gelastic seizures" - seizures manifesting w/ laughing/Other CNS Tumors)

>> Radiation

>> Trauma

>> Structural Abnormalities

-Sx/PE:

> Boys = LARGER TESTICLES for age

-Dx:

Bone Age = ADVANCED

Labs

> FSH/LH = HIGH for age (normal for those old enough for puberty)

> Test/Est = HIGH for age (normal for those old enough for puberty)

MRI = Look for CNS lesion

-Tx: CONSTANT GnRH receptor agonist (Leuprolide injection, Histrelin Implant)

-Prog:

McCune Albright Syndrome

Define Condition:

Activating mutation to the GNAS gene results in constant activation of (potentially) several G protein-coupled hormone receptors

-Path:

> Affects FSH & LH receptors --> inappropriate secretion of Testosterone or Estrogen

> TSH/GHRH/ACTH receptor activation --> Hyperthyroidism, GH Excess, Cortisol Excess

-Sx/PE:

> Precocious Puberty

>> Larger Testicles for age

> Cafe-au-lait patches w/ irregular borders (Coast of Maine borders) that "respect the midline"

> Fibrous dysplasia (normal bones replaced by fibrous connective tissue and poorly formed trabecular bone) affecting multiple bones

-Dx:

Labs

> FSH/LH = LOW (constant and abnormal state of activation b/c of negative feedback)

> Test/Est = HIGH

Bone Age = ADVANCED

Molecular DNA Analysis

-Tx: For PUBERTY Issue

> Girls = Aromatase inhibitors, Estrogen Blockage

> Boys = Aromatase inhibitors, Antiandrogens

-Prog:

Hormone-secreting Tumor

Define Condition:

A tumor is autonomously secreting testosterone or estrogen, resulting in secondary sexual characteristics

-Path:

> Girls = Granulosa cell tumor (in ovary)

> Boys = Leydig cell tumor (in testicle)

-Sx/PE:

> Palpable mass on testicular exam (boys) or on abdominal exam (girls)

>> Other gonad (w/o tumor) will be SMALLER (no FSH/LH to stimulate)

-Dx:

Labs

> FSH/LH = LOW

> Test/Est = HIGH

Imaging (US, CT) = Mass

-Tx: Surgical excision

-Prog:

Exogenous exposure

Define Condition:

Child exposed to substance that causes pubertal development

-Hx/Path:

> Test/Est Topical Applications

> Lavender/Tea Tree Oil (Weak Estrogen activity --> Breast Development)

-Dx:

Labs

> FSH/LH = LOW

> Test/Est (if offending agent) = HIGH

-Tx: Remove offending agents

Congenital Adrenal Hyperplasia (CAH)

Define Condition:

-Path: Causes androgenic pubertal features

-Sx/PE:

> Axillary Hair

> Pubic Hair

> Acne

> Deep voice

Galactorrhea

Define Condition:

Excessive or inappropriate discharge of milk from the nipple

-Hx:

> Idiopathic (Normal Prolactin Concentration)

> Secondary (Hyperprolactinemia)

>> Pregnancy

>> Lactotroph adenoma (Prolactinoma)

>> Hypothyroidism

>> Medication induced

Pregnancy

Define Cause of Galactorrhea:

When PL increases physiologically during this period and may also be INCREASED d/t increased Estrogen levels

-Path: Placenta is primary source of estrogen biosynthesis during pregnancy

-Dx: Urine Pregnancy Test

Lactotroph adenoma (prolactinoma)

Define Cause of Galactorrhea:

Uncontrolled expansion of prolactin secreting cell in pituitary --> Functional Adenoma that secretes EXCESSIVE prolactin

-Hx: WOMEN from 20-40 y/o (also males, any age)

-Path: PL Suppresses GnRH secretion --> Suppress Estrogen and Testosterone

-Sx/PE:

> Headaches

> Visual Impairment (compression of optic chiasm --> Bitemporal Hemianopsia)

> Premeno Females =

>> Oligomenorrhea/Amenorrhea

>> Inferility

>> Hot Flashes

>> Vaginal Dryness

>> Low Bone Density

>> GALACTORRHEA

> Postmeno Females = No Consequences (stopped making estrogen anyway)

>> GALACTORRHEA

> Men =

>> Impotence

>> Infertility

>> Fatigue

>> Gynecomastia

>> Diminished libido

>> (+/-) GALACTORRHEA

-Dx: MRI of Brain

-Tx:

> 1st = Dopamine Agonist (Cabergoline or Bromocriptine)

>> Activation of the dopamine receptor on the lactotroph cell inhibits PL release and reduces the size of the adenoma

>> Efficacy = 90%

>> Adenoma may shrink enough to d/c Treatment

> 2nd = Transphenoidal Surgery

>> If no response/no tolerance to D2 Agonist

Multiple Endocrine Neoplasia Type 1 (MEN1)

Define Cause of Galactorrhea:

A condition caused by a AUTOSOMAL DOMINANT mutation to the gene on a tumor suppressor on chromosome 11, associated with several endocrine tumors

-Hx: 1 to 10 per 100,000 individuals

-Hx/Path:

> Pituitary Adenoma = PLoma (20%), GH adenoma (5%)

> Parathyroid Adenoma = By Age 50 in 100%

> Pancreatic Tumors = Gastrinoma (30-40%), Insulinomas (100%), Glucagonomas (3%), Somatostatinomas (<1%)

-Dx:

Criteria

> TWO of classic tumors

> FHx of Condition + ONE of classic tumors

GENE TESTING

-Tx:

> Periodic Screening

> Tx of Tumor

Hypothyroidism

Define Cause of Galactorrhea:

-Path: Low T3/T4 --> High TRH (feedback) ==> PL Secretion

-Hx: Uncommon

-Sx/PE:

> Bradycardia

> HTN (Inc PVR)

> Wt Gain

> Non-pitting edema (infiltration of skin w/ glycosaminoglycans)

> Diminished DTRs

> ENLARGED THYROID GLAND (High TSH stimulates growth)

-Dx:

Labs

> T3/T4 = LOW

> PL = HIGH

-Tx: TH Replacement

Medication-Induced Hyperprolactinemia

Define Condition:

-Hx/Path: Use of...

> D2 Agonists (Antipsychotics, Metoclopramide) = Blocks Dopamine receptor on pituitary gland --> Can't inhibit PL secretion

> TCAs

> Verapamil

-Dx:

Labs

> PL = HIGH (Not High enough to induce Galactorrhea

-Tx: Remove offending agent

Idiopathic Galactorrhea

Define Cause of Galactorrhea:

-Dx:

Labs

> PL = Normal

-Tx: Reassurance or D2 Agonist (if bothersome)