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Secondary Adrenal Insufficiency


Ashley B. Grossman

, MD, University of Oxford; Fellow, Green-Templeton College

Reviewed/Revised May 2022 | Modified Sep 2022
Topic Resources

Secondary adrenal insufficiency is adrenal hypofunction due to a lack of adrenocorticotropic hormone (ACTH). Symptoms are the same as for Addison disease Addison Disease Addison disease is an insidious, usually progressive hypofunctioning of the adrenal cortex. It causes various symptoms, including hypotension and hyperpigmentation, and can lead to adrenal crisis... read more Addison Disease and include fatigue, weakness, weight loss, nausea, vomiting, and diarrhea, but there is usually less hypovolemia. Diagnosis is clinical and by laboratory findings, including low plasma ACTH with low plasma cortisol. Treatment depends on the cause but generally includes hydrocortisone.

Secondary adrenal insufficiency may occur in

  • Panhypopituitarism

  • Isolated failure of adrenocorticotropic hormone (ACTH) production

  • Patients receiving corticosteroids (by any route, including high doses of inhaled, intra-articular, or topical corticosteroids)

  • Patients who have stopped taking corticosteroids

Inadequate ACTH can also result from failure of the hypothalamus to stimulate pituitary ACTH production, which is sometimes called tertiary adrenal insufficiency.

Panhypopituitarism Symptoms and Signs may occur secondary to pituitary tumors, various other tumors, granulomas, and, rarely, infection or trauma that destroys pituitary tissue. In younger people, panhypopituitarism may occur secondary to a craniopharyngioma.

Patients receiving corticosteroids for > 4 weeks may have insufficient ACTH secretion during metabolic stress to stimulate the adrenals to produce adequate quantities of corticosteroids, or they may have atrophic adrenals that are unresponsive to ACTH. These problems may persist for up to 1 year after corticosteroid treatment is stopped and may need to be continued for an indeterminate period of time.

Symptoms and Signs of Secondary Adrenal Insufficiency

Symptoms and signs are similar to those of Addison disease Symptoms and Signs Addison disease is an insidious, usually progressive hypofunctioning of the adrenal cortex. It causes various symptoms, including hypotension and hyperpigmentation, and can lead to adrenal crisis... read more Symptoms and Signs and include fatigue, weakness, weight loss, nausea, vomiting, and diarrhea. Differentiating clinical or general laboratory features include the absence of hyperpigmentation and relatively normal electrolyte and BUN (blood urea nitrogen) levels; hyponatremia, if it occurs, is usually dilutional.

Patients with panhypopituitarism have depressed thyroid and gonadal function and hypoglycemia Hypoglycemia Hypoglycemia, or low plasma glucose level can result in sympathetic nervous system stimulation and central nervous system dysfunction. In patients with diabetes who take insulin or antihyperglycemic... read more . Coma may supervene when symptomatic secondary adrenal insufficiency occurs. Adrenal crisis is especially likely if a patient is treated for a single endocrine gland problem, particularly with thyroxine, without hydrocortisone replacement.

Diagnosis of Secondary Adrenal Insufficiency

  • Serum cortisol

  • Serum adrenocorticotropic hormone (ACTH)

  • ACTH stimulation testing

  • Central nervous system imaging

Tests to differentiate primary and secondary adrenal insufficiency are discussed under Addison disease Diagnosis Addison disease is an insidious, usually progressive hypofunctioning of the adrenal cortex. It causes various symptoms, including hypotension and hyperpigmentation, and can lead to adrenal crisis... read more Diagnosis . Patients with confirmed secondary adrenal insufficiency (see table ) should have CT or MRI of the brain to rule out a pituitary tumor or pituitary atrophy.


Adequacy of the hypothalamic-pituitary-adrenal axis Overview of the Endocrine System The endocrine system coordinates functioning between different organs through hormones, which are chemicals released into the bloodstream from specific types of cells within endocrine (ductless)... read more during tapering or after stopping long-term corticosteroid treatment can be determined by injecting cosyntropin 250 mcg IV or IM. After 30 minutes, serum cortisol should be > 20 mcg/dL (> 552 nmol/L); specific levels vary somewhat depending on the laboratory assay in use. An insulin stress test to induce hypoglycemia and a rise in cortisol is the standard for testing integrity of the hypothalamic-pituitary-adrenal axis in many centers but careful monitoring is required to avoid severe prolonged hypoglycemia.

The corticotropin-releasing hormone (CRH) test can be used to distinguish between hypothalamic and pituitary causes but is rarely used in clinical practice. After administration of CRH 100 mcg (or 1 mcg/kg) IV, the normal response is a rise of plasma ACTH of 30 to 40 pg/mL (6.6 to 8.8 pmol/L); patients with pituitary failure do not respond, whereas those with hypothalamic disease usually do.

Treatment of Secondary Adrenal Insufficiency

  • Hydrocortisone or prednisone/prednisolone

  • Fludrocortisone not indicated

  • Dose increase during intercurrent illness

Glucocorticoid replacement is similar to that described for Addison disease Treatment Addison disease is an insidious, usually progressive hypofunctioning of the adrenal cortex. It causes various symptoms, including hypotension and hyperpigmentation, and can lead to adrenal crisis... read more Treatment . Each case varies regarding the type and degree of specific hormone deficiencies. Normally, cortisol is secreted maximally in the early morning and minimally at night. Thus, hydrocortisone (identical to cortisol) is given in 2 or 3 divided doses with a typical total daily dose of 15 to 20 mg. One regimen gives half the total in the morning, and the remaining half split between lunchtime and early evening (eg, 10 mg, 5 mg, 5 mg). Others give two-thirds in the morning and one-third in the evening. Doses immediately before bed should generally be avoided because they may cause insomnia. Alternatively, prednisone or prednisolone 4 to 5 mg orally in the morning and possibly an additional 2.5 mg orally in the evening may be used. During acute febrile illness or after trauma, patients receiving corticosteroids for nonendocrine disorders may require supplemental doses to augment their endogenous hydrocortisone production.

Fludrocortisone is not required because the intact adrenals produce aldosterone.

Key Points

  • Secondary adrenal insufficiency involves adrenocorticotropic hormone (ACTH) deficiency due to pituitary or, less often, hypothalamic causes (including suppression by long-term corticosteroid use).

  • Other endocrine deficiencies (eg, hypothyroidism, growth hormone deficiency) may coexist.

  • Unlike in Addison disease, hyperpigmentation does not occur and serum sodium and potassium levels are relatively normal.

  • ACTH and cortisol levels both are low.

  • Glucocorticoid replacement is required, but mineralocorticoids (eg, fludrocortisone) are not necessary.

Drugs Mentioned In This Article

Drug Name Select Trade
A-Hydrocort, Ala-Cort, Ala-Scalp, Alkindi, Anucort-HC, Anumed-HC, Anusol HC, Aquaphor Children's Itch Relief, Aquaphor Itch Relief, Balneol for Her, Caldecort , Cetacort, Colocort , Cortaid, Cortaid Advanced, Cortaid Intensive Therapy, Cortaid Sensitive Skin, CortAlo, Cortef, Cortenema, Corticaine, Corticool, Cortifoam, Cortizone-10, Cortizone-10 Cooling Relief, Cortizone-10 External Itch Relief, Cortizone-10 Intensive Healing, Cortizone-10 Plus, Cortizone-10 Quick Shot, Cortizone-5 , Dermarest Dricort, Dermarest Eczema, Dermarest Itch Relief, Encort, First - Hydrocortisone, Gly-Cort , GRx HiCort, Hemmorex-HC, Hemorrhoidal-HC, Hemril , Hycort, Hydro Skin, Hydrocortisone in Absorbase, Hydrocortone, Hydroskin , Hydroxym, Hytone, Instacort, Lacticare HC, Locoid, Locoid Lipocream, MiCort-HC , Monistat Complete Care Instant Itch Relief Cream, Neosporin Eczema, NuCort , Nutracort, NuZon, Pandel, Penecort, Preparation H Hydrocortisone, Proctocort, Proctocream-HC, Procto-Kit, Procto-Med HC , Procto-Pak, Proctosert HC , Proctosol-HC, Proctozone-HC, Rectacort HC, Rectasol-HC, Rederm, Sarnol-HC, Scalacort, Scalpicin Anti-Itch, Solu-Cortef, Texacort, Tucks HC, Vagisil Anti-Itch, Walgreens Intensive Healing, Westcort
Aluvea , BP-50% Urea , BP-K50, Carmol, CEM-Urea, Cerovel, DermacinRx Urea, Epimide-50, Gord Urea, Gordons Urea, Hydro 35 , Hydro 40, Kerafoam, Kerafoam 42, Keralac, Keralac Nailstik, Keratol, Keratol Plus, Kerol, Kerol AD, Kerol ZX, Latrix, Mectalyte, Nutraplus, RE Urea 40, RE Urea 50 , Rea Lo, Remeven, RE-U40, RYNODERM , U40, U-Kera, Ultra Mide 25, Ultralytic-2, Umecta, Umecta Nail Film, URALISS, Uramaxin , Uramaxin GT, Urea, Ureacin-10, Ureacin-20, Urealac , Ureaphil, Uredeb, URE-K , Uremez-40, Ure-Na, Uresol, Utopic, Vanamide, Xurea, X-VIATE
Deltasone, Predone, RAYOS, Sterapred, Sterapred DS
AK-Pred, AsmalPred, Econopred, Econopred Plus, Flo-Pred, Hydeltrasol, Inflamase Forte, Inflamase Mild, Millipred , Millipred DP, Millipred DP 12-Day, Millipred DP 6 Day, Ocu-Pred , Ocu-Pred A, Ocu-Pred Forte, Omnipred, Orapred, Orapred ODT, Pediapred, Pred Mild, Predalone, Pred-Forte, Prednoral, Pred-Phosphate , Prelone, Veripred-20
NOTE: This is the Professional Version. CONSUMERS: View Consumer Version
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