Congenital adrenal hyperplasia

This page contains general information about Congenital adrenal hyperplasia. For more information on specific types, please visit the pages on 21-hydroxylase deficiency, 17a-Hydroxylase deficiency, 11β-hydroxylase deficiency, 3-beta-hydroxysteroid dehydrogenase, Cytochrome P450-oxidoreductase (POR) deficiency (ORD), congenital lipoid adrenal hyperplasia, cholesterol side-chain cleavage enzyme deficiency .

Congenital adrenal hyperplasia main page
Overview
Classification 21-hydroxylase deficiency
11β-hydroxylase deficiency
17 alpha-hydroxylase deficiency
3 beta-hydroxysteroid dehydrogenase deficiency
Cytochrome P450-oxidoreductase (POR) deficiency (ORD)
Lipoid congenital adrenal hyperplasia
Differential Diagnosis

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Mehrian Jafarizade, M.D [2]

Synonyms and keywords: Congenital adrenal hyperplasia, CAH, Adrenal hyperplasia

Overview

Classification

Congenital adrenal hyperplasia is classified into seven types based on the genetic causes that lead to hyperplasia and hormonal imbalance.

• 21-hydroxylase deficiency,
• 17a-Hydroxylase deficiency,
• 11β-hydroxylase deficiency,
• 3-beta-hydroxysteroid dehydrogenase,
• Cytochrome P450-oxidoreductase (POR) deficiency (ORD),
• Congenital lipoid adrenal hyperplasia,
• Cholesterol side-chain cleavage enzyme deficiency

Differential diagnosis

Disease	History and symptoms					Laboratory findings								Additional findings
21-hydroxylase deficiency	+	+	+	+	-	↑	↑	Normal	Normal	N/↑	Normal	↓	Normal
17a-Hydroxylase deficiency	+	+	+	+	-	↑	↑	Normal	Normal	↑	Normal	Normal	↑	Acanthosis nigricans
11β-hydroxylase deficiency	+	+	+	-	+	↑	↑	Normal	Normal	↑	Normal	Normal	N	-
3-beta-hydroxysteroid dehydrogenase	+	+	-	-	-	Normal	Normal	Normal	↓	Normal	Normal	Normal	Normal	-
Cytochrome P450-oxidoreductase (POR) deficiency (ORD)	+	+	-	-	-	Normal	Normal	Normal	↑	Normal	Normal	Normal	Normal	-
Congenital lipoid adrenal hyperplasia	-	-	-	-	-	↑	↑	Normal	Normal	↑	Normal	Normal	N/↑	In hospitalized patients especially in ICU and CCU
Cholesterol side-chain cleavage enzyme deficiency	+	-	-	-	+	↑	↑	Normal	Normal	↑	↑	N/↑	N/↑	Acanthosis nigricans,

Complications

Complications of diabetes mellitus may be classified as acute or chronic. Acute complications of diabetes mellitus may occur in type 1, type 2, or gestational diabetes. Chronic complications of diabetes mellitus are more likely to occur in long standing type 1 or type 2 diabetes and may be further classified as macrovascular, microvascular, or other (unspecified etiology) as follows:

Acute complications

They include diabetic ketoacidosis (DKA) and Hyperosmolar hyperglycemic state (HHS). DKA could be the presenting feature of type 1 diabetes and it is more common in type 1 diabetes although, it is sometimes seen in type 2 diabetic patients. HHS is mostly seen in the elderly and it is more common in type 2 diabetes.

Chronic complications

Macrovascular

• Coronary heart disease
• Peripheral arterial disease
• Cerebrovascular disease

Microvascular

Ophthalmic

• Retinopathy (nonproliferative/proliferative)
• Macular edema

Neuropathy

• Sensory and motor (mono- and polyneuropathy)
• Autonomic neuropathy

Nephropathy

• Albuminuria and declining renal function

Other organs

• Gastrointestinal (gastroparesis, diarrhea)
• Genitourinary (uropathy/sexual dysfunction)
• Dermatologic
• Infectious
• Cataracts
• Glaucoma
• Periodontal disease
• Hearing loss

Complications of gestational diabetes differs from type 1 and type 2 diabetes primarily due to its pregnancy-specific effects on the mother as well as its effects on the fetus.

For more information on maternal complications of gestational diabetes click here.

For more information on fetal complications of gestational diabetes click here.

Screening

Diabetes mellitus type 1

According to the American Diabetic Association, screening for type 1 DM is not recommended.

Diabetes mellitus type 2

Diabetes screening is recommended for many people at various stages of life, and for those with any of several risk factors. American Diabetes Association Recommendations for Diabetes Screening include:

• The general population should be screened every 3 years, beginning at age 45 (especially if their BMI>25kg/m2).
• Younger individuals should be screened if they have BMI>25kg/m2 and at least one of the following risk factors:
  • Sedentary life style
  • 1st degree relative with DM
  • African American, Native American, Latino, Asian American, Pacific Islander
  • Low HDL-C
  • History of gestational DM
  • Polycystic ovary syndrome
  • Vascular disease

To test for type 2 diabetes, fasting plasma glucose, 2-h plasma glucose after 75-g oral glucose tolerance test, and HbA1C are equally appropriate.

Gestational diabetes

All pregnant women should be screened for gestational diabetes in 24-28 weeks with 50 gram glucose test. Measurements greater than 130 mg/dL are considered positive and should proceed to 100 gram glucose test for diagnosis. High risk mothers should be screened as early as the first prenatal visit. These risk factors include:

• A family history of diabetes especially in first degree relatives
• Maternal age >25 yrs
• Certain ethnic groups (such as Native American, Hispanic-American, African-American, South or East Asian, Pacific Islander)
• Body mass index greater than 25 kg/m²
• Gestational diabetes or impaired glucose tolerance test in previous pregnancies
• Previous delivery of a baby >9 pounds
• Personal history of impaired glucose tolerance or impared fasting glucose (pre-diabetes)
• Glycosuria at the first prenatal visit
• Certain medical conditions (such as metabolic syndrome, polycystic ovary syndrome (PCOS), current use of glucocorticoids, hypertension)
• Previous history of unexplained miscarriage or stillbirth
• Smoking doubles the risk of gestational diabetes
• Multiple gestation
• Genetic predisposition (.e.g. glucokinase mutation)

Diagnosis

Diabetes mellitus type 1 and type 2

A fasting plasma glucose (FPG) <5.6 mmol/L (100 mg/dL), a plasma glucose <140 mg/dL (11.1 mmol/L) following an oral glucose challenge and an HbA1c <5.7% are considered normal.
Diagnostic criteria for DM are:

• Symptoms of diabetes plus random blood glucose concentration ≥11.1 mmol/L (200 mg/dL)^† OR
• Fasting plasma glucose ≥7.0 mmol/L (126 mg/dL)^‡ OR
• Hemoglobin A1c ≥ 6.5% OR
• 2-h plasma glucose ≥11.1 mmol/L (200 mg/dL) during an oral glucose tolerance test^¶

Note:
†:Random is defined as without regard to time since the last meal.

‡:Fasting is defined as no caloric intake for at least 8 h.

¶:The test should be performed using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water, not recommended for routine clinical use.

American Diabetes Association Diabetes Diagnostic Criteria 2017 (DO NOT EDIT)

Criteria for the diagnosis of diabetes
FPG ≥126 mg/dL (7.0 mmol/L). Fasting is defined as no caloric intake for at least 8 h.
OR
2-h Plasma Glucose (PG) ≥200 mg/dL (11.1 mmol/L) during an OGTT. The test should be performed as described by the WHO, using a glucose load containing the equivalent of 75 g anhydrous glucose dissolved in water.
OR
A1C ≥6.5% (48 mmol/mol).
OR
In a patient with classic symptoms of hyperglycemia or hyperglycemic crisis, a random plasma glucose ≥200 mg/dL (11.1 mmol/L).

Gestational diabetes

There are 2 strategies to confirm the GDM diagnosis.

• One-step 75-g Oral glucose tolerance test (OGTT)

OR

• Two-step approach with a 50-g (nonfasting) screen followed by a 100-g OGTT for those who screen positive.

One Step Strategy=

Perform a 75 g glucose tolerance test in 24-28 weeks of pregnancy and read the measures 1 h and 2 h after glucose ingestion as well as fasting glucose. The OGTT should be performed in the morning after an overnight fast of at least 8 h. The diagnosis of GDM is made when any of the following plasma glucose values are met or exceeded:

• Fasting: 92 mg/dL (5.1 mmol/L)
• 1 h: 180 mg/dL (10.0 mmol/L)
• 2 h: 153 mg/dL (8.5 mmol/L)

Two Step Strategy

In this approach, screening with a 1 h 50-g glucose load test (GLT) followed by a 3 h 100-g OGTT for those who screen positive.

The diagnosis of GDM is made when at least 2 out of 4 measures of 3 h 100-g OGTT became abnormal.

• The following table summarizes the diagnostic approach for gestational diabetes.

	Cut off (mg/dl)
	Fasting	1 Hour	2 Hour	3 Hour
One step test 2 hour 75 g glucose tolerance test	92	180	153	----
Two step test 1 hour 50 g screening test	----	140	----	----
3 hour 100 g test if screening test became positive Carpenter/Coustan approach	95	180	155	140
National Diabetes Data Group (NDDG) approach	105	190	165	145

Prevention

Life style modification is the mainstay of prevention of diabetes mellitus. It includes, changes in diet, weight reduction and exercise. The strongest evidence for diabetes prevention comes from the Diabetes Prevention Program (DPP). The DPP demonstrated that an intensive lifestyle intervention could reduce the incidence of type 2 diabetes by 58% over 3 years.

References