Treatment algorithm

Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups: see disclaimer

INITIAL

pituitary apoplexy

1st line – intravenous hydrocortisone

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INITIAL
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pituitary apoplexy
1st line – 

intravenous hydrocortisone

Acute severe hypopituitarism may occur with pituitary apoplexy (sudden spontaneous development of a haemorrhage into or infarction of a pre-existing adenoma). This may present with nausea, vomiting, fatigue, weakness, dizziness, and circulatory collapse secondary to acute loss of adrenocorticotrophic hormone. These patients should be treated presumptively for suspected acute cortisol deficiency with hydrocortisone.

Primary options

hydrocortisone: children: consult specialist for guidance on dose; adults: 50-100 mg intravenously every 6-8 hours, or 0.18 mg/kg/hour intravenous infusion over 24 hours

ONGOING

hypopituitarism

1st line – treatment of any correctable underlying cause

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ONGOING
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hypopituitarism
1st line – 

treatment of any correctable underlying cause

Where possible, the underlying cause must be addressed. Some causes, such as prior surgery or radiotherapy, are not correctable and treatment thus focuses on replacing the target hormones.

Plus – maintenance oral corticosteroids

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ONGOING
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hypopituitarism
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with adrenocorticotrophic hormone deficiency
Plus – 

maintenance oral corticosteroids

Treatment recommended for ALL patients in selected patient group

Lifelong glucocorticoid replacement is a balance between avoiding long-term complications of over-treatment (iatrogenic Cushing syndrome) and avoiding under-replacement, which can be life-threatening.[54] The efficacy of glucocorticoid replacement is assessed clinically.

There is no universal consensus on the appropriate dosing or timing of glucocorticoid replacement. The normal daily cortisol production rate is equivalent to the oral administration of hydrocortisone 15-20 mg/day, given as 2 or 3 divided doses (for adults). The optimal dosing regimen of hydrocortisone is 10 mg on rising, 5 mg at lunchtime, and 5 mg in the early evening, but most people do well on 10 mg on rising and 5 mg in the early afternoon.[32][55] A specialist should be consulted for guidance on dosing for children.

For patients with hypophysitis associated with anti-cytotoxic T-lymphocyte antigen-4 (CTLA-4) immunotherapy (e.g., ipilimumab), high doses of corticosteroids to reduce inflammation and to preserve and reverse pituitary damage do not appear to improve hormonal recovery or improve survival, compared to physiological replacement doses of corticosteroids.[57] These patients are at risk for adrenal insufficiency long-term.[58] CTLA-4 inhibitor therapy may need to be interrupted or discontinued depending on the severity of hypophysitis.

Primary options

hydrocortisone: children: consult specialist for guidance on dose; adults: 15-20 mg/day orally given in 2-3 divided doses (e.g.,10 mg in the morning, 5 mg at noon, and 5 mg in the evening; or 10 mg in the morning and 5 mg in the early afternoon)

OR

prednisolone: children: consult specialist for guidance on dose; adults: 5 mg orally in the morning and 2.5 mg in the afternoon

Consider – intravenous or intramuscular corticosteroids for stress events

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ONGOING
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hypopituitarism
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with adrenocorticotrophic hormone deficiency
Consider – 

intravenous or intramuscular corticosteroids for stress events

Additional treatment recommended for SOME patients in selected patient group

Stress dosing with intravenous or intramuscular hydrocortisone is mandatory during major surgery, trauma, or severe illnesses. All patients should carry a steroid emergency card or bracelet/necklace with instructions about stress-related dose adjustments. A 2- to 3-fold increase in oral corticosteroid replacement is required during episodes of minor stress; this is also known as 'sick day' dosing.

If an adrenal crisis is suspected, patients should be given an immediate parenteral injection of hydrocortisone.

Primary options

hydrocortisone: children: consult specialist for guidance on dose; adults: 50-100 mg intravenously/intramuscularly every 6-8 hours, or 0.18 mg/kg/hour intravenous infusion over 24 hours

Plus – levothyroxine after full adrenal replacement

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ONGOING
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hypopituitarism
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with thyroid hormone deficiency
Plus – 

levothyroxine after full adrenal replacement

Treatment recommended for ALL patients in selected patient group

Secondary hypothyroidism is treated with replacement of thyroid hormone. It is vital that adrenocorticotrophic hormone deficiency is diagnosed and treated appropriately prior to initiating thyroid hormone in order not to provoke an adrenal crisis due to increased cortisol clearance.

The goal of treatment is a normal serum free thyroxine (FT4) value. Measurement of serum thyroid-stimulating hormone cannot be used as a guide to the adequacy of levothyroxine replacement therapy.

Cautious titration in older adults is important to avoid precipitating myocardial ischaemia.

Growth hormone (GH) replacement in a euthyroid patient can unmask central hypothyroidism. Additionally, patients who are on thyroid hormone placement and are started on GH replacement may require higher doses of thyroid hormone. It is important to check FT4 when GH therapy is being considered.[32]

Long-term over-replacement has been associated with an increased risk of atrial fibrillation and low bone mineral density.[59]

Primary options

levothyroxine: children: consult specialist for guidance on dose; adults (no coronary artery disease): 1.6 micrograms/kg/day orally, adjust dose according to FT4 levels; adults (elderly or coronary artery disease): 25 micrograms orally once daily initially, increase by 12.5 micrograms/day increments every 4-6 weeks according to FT4 levels

Plus – oestrogen

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ONGOING
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hypopituitarism
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female with gonadotrophin-releasing hormone deficiency: fertility not desired
Plus – 

oestrogen

Treatment recommended for ALL patients in selected patient group

Oestrogen therapy alleviates symptoms - namely, hot flushes - and prevents osteoporosis in women.[60] The majority of endocrinologists treat patients up to age 50 years.[7] In post-menopausal women, the risks and benefits of therapy need to be assessed and discussed with the patient.

Primary options

estradiol transdermal: adults: 0.025 to 0.05 mg/day patch once weekly

Secondary options

conjugated oestrogens: adults: 0.625 to 1.25 mg orally once daily for 25 days of cycle

Consider – progesterone

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ONGOING
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hypopituitarism
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female with gonadotrophin-releasing hormone deficiency: fertility not desired
Consider – 

progesterone

Additional treatment recommended for SOME patients in selected patient group

Progesterone must be given with oestrogen in women with a uterus to prevent unopposed oestrogenic stimulation of the endometrium.

Primary options

medroxyprogesterone: adults: 5-10 mg orally once daily on days 16-25 of cycle

Plus – gonadotrophins

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ONGOING
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hypopituitarism
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female with gonadotrophin-releasing hormone deficiency: fertility desired
Plus – 

gonadotrophins

Treatment recommended for ALL patients in selected patient group

In women with secondary hypogonadism who desire fertility, treatment with gonadotrophins is recommended.

These medications should only be utilised by experienced practitioners, and advice should be sought from a reproductive endocrinologist.

Plus – testosterone

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ONGOING
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hypopituitarism
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male with gonadotrophin-releasing hormone deficiency: fertility not desired
Plus – 

testosterone

Treatment recommended for ALL patients in selected patient group

Androgen replacement therapy is recommended in hypogonadal men as it has beneficial effects on mood, body composition, sexual function, and bone mineral density, if there are no contraindications.[32][45] Testosterone replacement is not recommended in patients planning fertility or in those with elevated prostate-specific antigen (PSA) levels, elevated haematocrit, severe untreated obstructive sleep apnoea, severe lower urinary tract symptoms, thrombophilia, uncontrolled heart failure, or myocardial infarction or stroke within the last 6 months.[45]

Testosterone replacement therapy is especially beneficial in males who have not initiated puberty by the age of 14 and in males with low testosterone levels due to hypothalamic-pituitary disease.[64] Caution should be exercised in the administration of exogenous testosterone to hypogonadal men over 65 years with multiple cardiovascular risk factors, as it has been shown to increase the rate of adverse cardiovascular events compared with placebo.[65]

Androgen replacement therapy for men is available as intramuscular injections of testosterone. However, the intramuscular formulation is associated with wide fluctuations in testosterone levels. Transdermal patches and gels, subcutaneous injections, and oral preparations are also available. These preparations offer more stable testosterone levels compared with the intramuscular route.

The adequacy of treatment is assessed by the patient's clinical response and serum testosterone levels, targeted to the mid-normal range.[45]

PSA, haematocrit, liver function tests, and lipid levels need to be monitored serially. Androgen replacement therapy is contraindicated in patients with prostate cancer and breast cancer.

Primary options

testosterone transdermal: adults: (1% gel) apply 50-100 mg once daily in the morning; (1.62% gel) apply 20.25 to 81 mg once daily in the morning; (2% gel) apply 10-70 mg once daily in the morning

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OR

testosterone transdermal: adults: (2 mg/day or 4 mg/day transdermal patch) 2-6 mg/day applied once daily at night

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OR

testosterone undecanoate: adults: 158-396 mg orally twice daily

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Secondary options

testosterone cipionate: adults: 50-400 mg intramuscularly every 2-4 weeks

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OR

testosterone enantate: adults: 250 mg intramuscularly every 2-3 weeks initially, followed by 250 mg every 3-6 weeks for maintenance therapy

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Plus – gonadotrophins

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ONGOING
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hypopituitarism
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male with gonadotrophin-releasing hormone deficiency: fertility desired
Plus – 

gonadotrophins

Treatment recommended for ALL patients in selected patient group

In men with secondary hypogonadism who desire fertility, treatment with gonadotrophins is recommended.

These medications should only be utilised by experienced practitioners, and advice should be sought from a specialist.

Plus – recombinant human growth hormone

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ONGOING
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hypopituitarism
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with growth hormone deficiency
Plus – 

recombinant human growth hormone

Treatment recommended for ALL patients in selected patient group

Growth hormone (GH) treatment should be encouraged in patients with severe clinical manifestations of GH deficiency such as fatigue, poor quality of life, truncal obesity, unfavourable lipid profile, low muscle mass or strength, and low bone mineral density. It is recommended that GH dosing be individualised independent of body weight, initially starting with a low dose and titrating up slowly to the minimal dose that normalises serum insulin-like growth factor-1 levels, without causing adverse side effects.[32][70]

Primary options

somatropin (recombinant): children and adults: dose depends on brand used; consult specialist for guidance on dose

Plus – desmopressin

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ONGOING
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hypopituitarism
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with antidiuretic hormone deficiency
Plus – 

desmopressin

Treatment recommended for ALL patients in selected patient group

Desmopressin is a synthetic analogue of antidiuretic hormone (ADH) and is the drug of choice for ADH replacement. It is available in oral, intranasal, and subcutaneous/intravenous preparations. Dosages vary widely with no relationship to age, sex, or weight.

Over-replacement leads to hyponatraemia and water intoxication; therefore, serum sodium levels should be checked after commencing therapy and on changing the dose.

Primary options

desmopressin nasal: children: consult specialist for guidance on dose; adults: 10 micrograms once daily at night initially, increase by 2.5 microgram/day increments, maximum 40 micrograms/day given in divided doses

OR

desmopressin: children: consult specialist for guidance on dose; adults: 0.05 mg orally twice daily, maximum 1.2 mg/day given in divided doses; 1-2 micrograms subcutaneously/intravenously twice daily

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Please note that formulations/routes and doses may differ between drug names and brands, drug formularies, or locations. Treatment recommendations are specific to patient groups. See disclaimer

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