Peptides Hormones · Supplementary · from Peptides Hormones

Case 1: Growth Hormone Deficiency in Adult

Patient Presentation

Demographics: 42-year-old male software developer

Chief Complaint: "I feel like I'm aging faster than I should. I've lost muscle, gained belly fat, and my energy is terrible."

History of Present Illness: The patient presents with a 3-year history of progressive body composition changes, fatigue, and diminished quality of life. He reports a 12 kg increase in truncal adiposity despite maintaining his exercise routine, along with noticeable loss of muscle mass in his arms and legs. He describes his energy as "running on empty," with an inability to sustain the physical and cognitive output he could 5 years ago.

He reports decreased exercise capacity, noting that his gym performance has declined substantially. Recovery from workouts takes 2-3 days compared to his previous 24-hour recovery time. He also describes dry, thinning skin, impaired sleep quality with reduced deep sleep phases, increased anxiety, social withdrawal, and diminished emotional resilience.

His symptoms began gradually after a traumatic brain injury sustained in a mountain biking accident 4 years ago, which involved a brief loss of consciousness (< 5 minutes) and a frontal contusion identified on CT at the time. He was managed conservatively and made a good neurological recovery but has noted progressive endocrine symptoms since.

Past Medical History:

• Traumatic brain injury (4 years ago, mild-moderate)
• Concussion history (2 prior sports-related concussions in college)
• No prior endocrine diagnoses

Medications:

• None currently
• Previously tried DHEA 50 mg daily (self-directed, minimal benefit)

Social History:

• Non-smoker, minimal alcohol
• Regular gym-goer (4x/week resistance training)
• Single, lives alone
• High-stress job but manages well
• 7 hours sleep per night but poor quality

Family History:

• Father: Type 2 diabetes
• Mother: Osteoporosis
• No family history of pituitary disease

Physical Examination

• Vital Signs: BP 118/74 mmHg, HR 72 bpm, RR 14, Temp 36.7°C, SpO2 99% RA, BMI 28.6, Waist circumference 98 cm
• General: Appears stated age, increased truncal adiposity with relatively thin extremities
• HEENT: Normal visual fields by confrontation, no papilledema
• Skin: Thin, dry skin with reduced turgor, fine wrinkles around eyes
• Cardiovascular: Regular rate and rhythm, no murmurs
• Abdomen: Central adiposity, soft, non-tender
• Musculoskeletal: Decreased muscle bulk in deltoids, biceps, and quadriceps relative to expected for activity level
• Neurological: Cranial nerves intact, no focal deficits, normal cognition on bedside testing

Workup and Results

Laboratory Studies:

Imaging/Additional Studies:

• MRI pituitary with contrast: Small pituitary gland (height 3.2 mm, lower limit of normal), partially empty sella, no adenoma or mass lesion, stalk midline
• DEXA body composition: Increased truncal fat, reduced appendicular lean mass index
• Carotid intima-media thickness: 0.82 mm (above 75th percentile for age, indicating subclinical atherosclerosis)
• Quality of Life Assessment (QoL-AGHDA): Score 18/25 (significant impairment)

Clinical Image

Diagram illustrating the somatotropic (GH-IGF-1) axis showing hypothalamic GHRH and somatostatin regulation of pituitary GH release, hepatic IGF-1 production, and the metabolic consequences of adult GH deficiency on body composition, cardiovascular health, bone density, and quality of life. Source: Educational illustration.

Diagnosis

Adult-Onset Growth Hormone Deficiency (AO-GHD) Secondary to Traumatic Brain Injury, with Metabolic Syndrome, Osteopenia, and Subclinical Atherosclerosis

Key Diagnostic Criteria:

• Low IGF-1 (88 ng/mL) below age-adjusted reference range
• Failed two dynamic stimulation tests: GHRH-arginine peak GH 4.2 ng/mL (cutoff > 11 for BMI 25-30) and ITT peak GH 3.1 ng/mL (cutoff > 5)
• Identified etiology: traumatic brain injury (TBI is recognized cause of hypopituitarism, GH axis most commonly affected)
• Partially empty sella on MRI consistent with pituitary atrophy
• Clinical phenotype of AO-GHD: increased truncal fat, decreased lean mass, dyslipidemia, osteopenia, impaired quality of life
• Other pituitary axes intact (cortisol response adequate on ITT, normal thyroid and gonadal function)

Treatment Plan

1. Growth hormone replacement therapy:

• Recombinant human GH (somatropin) starting dose 0.2 mg/day subcutaneous injection at bedtime (lower starting dose for males; females typically require higher doses)
• Titrate dose by 0.1-0.2 mg every 4-6 weeks based on IGF-1 levels (target mid-to-upper normal range for age) and clinical response
• Expected maintenance dose 0.4-0.8 mg/day
• Alternative: Somapacitan (long-acting GH analog) 1.5 mg/week SC for improved adherence if cost permits

1. Monitoring protocol:

• IGF-1 levels at 1, 3, 6, and 12 months, then every 6 months
• Fasting glucose, HbA1c, and insulin at 3 and 6 months (GH can worsen insulin resistance initially)
• Lipid panel at 6 months (expect improvement in LDL and total cholesterol)
• Free T4 at 3 and 6 months (GH can unmask central hypothyroidism by increasing T4-to-T3 conversion)
• DEXA body composition and bone density at 12 months
• Quality of life assessment (QoL-AGHDA) at 6 and 12 months

1. Metabolic optimization:

• Structured resistance training program (maintain current 4x/week, progressive overload)
• Dietary modification: increase protein to 1.6 g/kg/day, reduce refined carbohydrates, Mediterranean pattern
• Monitor glucose closely given pre-diabetes and GH-mediated insulin antagonism

1. Cardiovascular risk management:

• Address dyslipidemia (may improve with GH replacement, reassess statin need at 6 months)
• Repeat carotid IMT at 12 months

1. Side effect counseling: Arthralgia, peripheral edema, and carpal tunnel syndrome are common dose-dependent side effects; managed with dose reduction. Review symptoms at each visit.
2. Long-term screening: Annual pituitary hormone panel to monitor for evolution of additional axis deficits post-TBI

Key Learning Points

• Traumatic brain injury (even mild-moderate) is an underrecognized cause of hypopituitarism, with the GH axis being the most vulnerable; prevalence of GHD post-TBI ranges from 10-30% and can manifest months to years after injury
• Diagnosis of adult GHD requires a low IGF-1 combined with failure of at least one dynamic stimulation test (ITT remains gold standard; GHRH-arginine is acceptable alternative), with BMI-adjusted cutoffs for the GHRH-arginine test
• Adult GHD is associated with adverse metabolic profile (visceral obesity, dyslipidemia, insulin resistance), increased cardiovascular risk, reduced bone density, and significantly impaired quality of life that responds to GH replacement
• GH replacement can initially worsen glucose tolerance through insulin antagonism; careful monitoring is essential in patients with pre-existing insulin resistance or pre-diabetes
• GH treatment may unmask central hypothyroidism by enhancing peripheral conversion of T4 to T3, necessitating thyroid function monitoring during therapy initiation

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