Adrianne M. Cook, ND, FABNE
Subheadline
A case report illustrating how fatigue, weight gain, brain fog, metabolic dysfunction, and vasomotor symptoms initially attributed to menopause revealed underlying hypopituitarism, central adrenal insufficiency, and secondary hypothyroidism.
Short Description
This case report describes a 51-year-old woman whose worsening fatigue, weight gain, recurrent infections, insulin resistance, and menopausal symptoms were ultimately traced to pituitary hypophysitis rather than menopause alone. The case highlights the importance of comprehensive endocrine evaluation, trend analysis, and root-cause investigation when symptoms appear disproportionate to the expected menopausal transition.
Introduction
Fatigue, weight gain, brain fog, sleep disturbance, low libido, joint pain, insulin resistance and vasomotor symptoms are among the most common concerns seen in women during the menopausal transition. Because these symptoms are so prevalent, it is easy to attribute them primarily to ovarian hormone decline. While menopause is often a contributing factor, it is not always the entire story.
It can be tempting to focus on symptom management alone for peri-menopausal women.However, these symptoms can arise from dysfunction across multiple endocrine systems, not solely from estrogen deficiency. This case demonstrates how a familiar presentation of menopause and metabolic dysfunction can occasionally reflect a far more significant endocrine disorder. It highlights the importance of maintaining a broad clinical perspective and illustrates the value of comprehensive hormone assessment when symptoms appear disproportionate to the expected menopausal transition.
Case Presentation
A 51-year-old woman presented with hot flashes, lack of libido, dry skin, progressive fatigue, increasing weight gain (BMI 41.19), joint pain, brain fog and impaired concentration, and recurrent infections. She described feeling increasingly exhausted despite efforts to improve her health. Weight loss had become increasingly difficult, and she felt her overall health was moving in the wrong direction.
Her metabolic markers had continued to worsen despite treatment efforts. A prior trial of GLP-1 receptor agonist therapy had been discontinued because of poor tolerance and adverse effects resulting in a visit to the emergency department. She was actively pursuing bariatric surgery at the time of presentation due to ongoing concerns regarding weight and metabolic health and was referred to me by her nutritionist.
Like many women in midlife, several of her symptoms had initially been attributed tomenopause. Fatigue, weight gain, low libido and changes in body composition are commoncomplaints among women in their fifties. However, there were several aspects of herpresentation that suggested a more complex endocrine picture.
Looking Beyond Estrogen
In recent years, menopause management has increasingly emphasized symptom-guidedtreatment. While symptoms are essential to understanding a patient’s experience, they do not always identify the underlying cause. Symptoms commonly attributed to menopause—including fatigue, brain fog, weight gain, vasomotor symptoms, low libido, and joint pain—may also reflect dysfunction involving the thyroid, adrenal glands, pituitary gland, growth hormone axis, or glucose metabolism.
While routine hormone testing is not necessary for every menopausal patient, symptoms that appear disproportionate to the expected menopausal transition may warrant a broader evaluation. Depending on the clinical presentation, this may include assessment of thyroid function, morning cortisol, DHEA-S, testosterone by LC/MS, metabolic and insulin resistance markers, cardiovascular risk factors, iron status, and selected nutrient markers.
The goal is not to search for rare diagnoses. The goal is to understand the broader endocrine environment contributing to the patient’s symptoms.
Initial Laboratory Findings
Initial laboratory evaluation revealed several findings that were individually subtle butcollectively concerning. Laboratory testing was recommended as morning fasting assessment; however, the initial sample was reportedly collected at 11:17 AM while fasting.
| Marker | Initial Result |
|---|---|
| Hemoglobin A1c | 6.3% |
| Insulin | 33.4 |
| IR Score (NMR) | 75 |
| TSH | 2.21 |
| Free T4 | 0.81 |
| FSH | 29.4 |
| Estradiol | 14.1 |
| Testosterone | 18.8 |
| Morning Cortisol | 6.1 |
Morning cortisol (at 11:17am) was mildly below the reference range. Free T4 was low despite a normal TSH. Insulin resistance markers were elevated, and glycemic control appeared to be worsening.
None of these findings independently established a diagnosis. However, they suggested that her fatigue and declining health might not be explained by menopause alone.
Perhaps most importantly, the patient’s symptoms appeared disproportionate to what would typically be expected from menopause and insulin resistance alone. Her recurrent infections, worsening fatigue, increasing weight and inability to recover her vitality raised concern that another process might be contributing.
Rather than attributing her symptoms solely to menopause or metabolic dysfunction, repeat testing was ordered to better characterize the abnormalities and obtain earlier morning hormone assessment.
The Value of Trend Analysis
One of the most important lessons from this case was the value of following laboratory trends. Approximately three weeks later, repeat morning testing was performed. The patient was specifically instructed to schedule the laboratory draw near 8:00 AM, when cortisol and several pituitary-regulated hormones would typically be expected to be near their daily peak.
| Marker | Initial | Repeat |
|---|---|---|
| Cortisol AM | 6.1 | 1.2 |
| ACTH | — | 14 |
| FSH | 29.4 | 8.4 |
| Estradiol | 14.1 | 5.6 |
| Testosterone | 18.8 | 4.7 |
| IGF-1 | — | 94 |
| TSH | 2.21 | 3.33 |
| Free T4 | 0.81 | 1.08 |
Although the initial cortisol was drawn later in the morning, the subsequent value of 1.2 μg/dL obtained near 8:00 AM was particularly concerning because cortisol would normally be expected to be highest at that time of day.
Morning cortisol had fallen dramatically. ACTH remained inappropriately normal despite severe cortisol deficiency. Gonadotropins that had previously been within an expected menopausal range dropped significantly. Testosterone levels declined substantially, while IGF-1 was low-normal.
The laboratory picture was no longer consistent with isolated ovarian aging. Instead, multiple hormonal systems appeared to be deteriorating simultaneously. Pituitary hormones that would normally be expected to rise in response to falling target hormones were failing to do so.
At this point, the clinical question shifted. Rather than asking how to manage menopausal symptoms, the more important question became: What is causing failure across multiple endocrine axes?
Recognizing Central Adrenal Insufficiency
Among all of the laboratory findings, the cortisol results were the most concerning.
Cortisol is essential for blood pressure regulation, immune function, glucose homeostasis, and the physiologic response to stress. In this patient, severe cortisol deficiency likely contributed to recurrent infections and impaired recovery. The markedly low cortisol level with an inappropriately normal ACTH suggested central adrenal insufficiency originating at the level of the pituitary.
Her history of recurrent infections added further concern. Patients with severe cortisol deficiency may have difficulty mounting an appropriate physiologic response to illness, placing them at risk for adrenal crisis.
Given the rapid progression of laboratory abnormalities and the potential severity of untreated adrenal insufficiency, emergency department evaluation was recommended to get STAT imaging and specialist on board immediately.
Evidence of Secondary Hypothyroidism
In addition to adrenal dysfunction, the patient’s thyroid markers suggested evolving centralhypothyroidism. Free T4 remained below optimal range despite a TSH that was normal and therefore physiologically inappropriate for the degree of thyroid hormone deficiency. While a normal TSH is often reassuring in primary care settings, it can be misleading when pituitary dysfunction is present.
This pattern differs from primary hypothyroidism, in which TSH is typically elevated in response to falling thyroid hormone levels. In central hypothyroidism, pituitary dysfunction prevents an adequate TSH response, resulting in thyroid hormone deficiency despite apparently “normal” thyroid screening results.
This finding reinforced the importance of evaluating more than TSH alone when patients present with persistent fatigue, weight changes, metabolic dysfunction, and symptoms commonly attributed to menopause or hypothyroidism. The coexistence of central adrenal insufficiency, secondary hypothyroidism, declining gonadotropins, and IGF-1 further strengthened the suspicion of pituitary pathology and reinforced the need for imaging.
Diagnosis: Pituitary Hypophysitis
Given concern for evolving hypopituitarism, the patient was referred for emergency evaluation to expedite pituitary imaging and endocrine consultation. MRI revealed pituitary hypophysitis, an inflammatory condition affecting the pituitary gland. The diagnosis provided a unifying explanation for the patient’s progressive fatigue, recurrent infections, worsening metabolic dysfunction, and evolving deficiencies across multipleendocrine axes.
Hypophysitis is uncommon and can present with nonspecific symptoms such as fatigue,headache, weakness, hormonal dysfunction, and metabolic changes. Because the pituitary regulates multiple endocrine systems, inflammation can result in deficiencies affecting ACTH, thyroid-stimulating hormone, gonadotropins, growth hormone, and vasopressin.
The patient was started on hydrocortisone replacement therapy and referred to endocrinology for ongoing management. She was educated regarding stress-dose (“sick day”) glucocorticoid protocols. Ongoing co-management included thyroid hormone replacement as well as treatment of persistent androgen and menopausal hormone deficiencies.
Fortunately, recognition of the condition occurred before progression to adrenal crisis and prior to her planned bariatric surgery. This case underscores the importance of considering endocrine causes of obesity and metabolic dysfunction before proceeding with irreversible interventions.
Why This Case Matters
The significance of this case is not that hypophysitis is common. Most clinicians will rarelyencounter this diagnosis. Rather, the lesson lies in the diagnostic process. What initially appeared to be obesity, insulin resistance, menopause, fatigue, and recurrent infections ultimately reflected a single process affecting multiple endocrine systems simultaneously. The diagnosis of hypophysitis provided a unifying explanation for the patient’s metabolic dysfunction, hormonal deficiencies, and impaired physiologic response to stress. This case serves as a reminder of the naturopathic principle Tolle Causam—treat the cause. Identifying the underlying pituitary pathology allowed treatment to be directed toward the root cause rather than managing each symptom in isolation.
The Endocrine Orchestra
I often explain endocrine physiology using the analogy of an orchestra. Estrogen is oneinstrument, but the pituitary serves as the conductor. Dysfunction at the level of the conductor can affect multiple hormonal systems simultaneously. This case illustrates how symptoms attributed to a single hormone deficiency may instead reflect broader endocrine dysfunction.
Clinical Pearls
Several practical lessons emerged from this experience:
- Menopause should not automatically be assumed to explain all symptoms in midlifewomen.
- Comprehensive hormone assessment can identify abnormalities outside the ovarian axis.
- Morning cortisol remains an important consideration in patients with severe fatigue,recurrent illness, or unexplained endocrine symptoms.
- Laboratory trends are often more informative than isolated laboratory values.
- Failure of expected metabolic interventions should prompt reconsideration of theunderlying diagnosis.
- Patients considering bariatric surgery may benefit from a comprehensive endocrineevaluation when symptoms extend beyond weight concerns alone.
- Collaboration between primary care providers, naturopathic physicians, endocrinologists, and emergency medicine physicians can facilitate timely diagnosis and treatment.
Conclusion
Most patients presenting with menopausal symptoms will not have a rare endocrine disorder. However, this case serves as a reminder of the naturopathic principle Tolle Causam—to seek and address the underlying cause. What initially appeared to be a familiar presentation of menopause and metabolic dysfunction ultimately reflected pituitary hypophysitis with central adrenal insufficiency and secondary hypothyroidism.The lesson is not that every patient has a rare disease. The lesson is that maintaining a broad clinical perspective allows us to recognize the patients who do.
Resources
The North American Menopause Society (NAMS). The 2022 Hormone Therapy PositionStatement of The North American Menopause Society. Menopause: The Journal of TheNorth American Menopause Society Vol. 29, No. 7, pp. 767-794
Bornstein SR, Allolio B, Arlt W, et al. Diagnosis and Treatment of Primary AdrenalInsufficiency: An Endocrine Society Clinical Practice Guideline. J Clin EndocrinolMetab. 2016;101(2):364-89.
Gupta V, Lee M. Central hypothyroidism. Indian J Endocrinol Metab. 201;15(Suppl2):S99-S106.
Caranci F, Leone G, Ponsiglione A, et al. Imaging findings in hypophysitis: a review.Radiol Med. 2020;125(3):319-328.
Fleseriu M, Hashim IA, Karavitaki N, et al. Hormonal Replacement in Hypopituitarismin Adults: An Endocrine Society Clinical Practice Guideline. J Clin Endocrinol Metab.2016;101(11):3888-3921.
Author Bio:
Dr. Adrianne Cook is a licensed naturopathic physician practicing in Washington State withnearly two decades of clinical experience and practice focused on hormone health andendocrinology. She earned a Bachelor’s degree in Nutritional Sciences in 1997 from theUniversity of New Hampshire and graduated from Bastyr University in 2007. She achievedFABNE certification in 2025 and serves on the EndoANP Board.
Her clinical practice focuses on hormone health, including menopause, thyroid, adrenal, and metabolic disorders. She emphasizes individualized, systems-based care and physiologic hormone prescribing to support long-term patient health. Her work integrates nutrition, functional medicine, and advanced laboratory assessment within a comprehensive endocrine care model.
