Allison Sayre, MSN, WHNP and Corey Schuler, PhD, FNP, CNS
Thyroid symptoms are often discussed through the lens of laboratory values, while mood changes are frequently treated as separate or secondary concerns. Cortisol is usually mentioned only in the context of stress. Yet these systems are not independent. The hypothalamic-pituitary-adrenal axis and the hypothalamic-pituitary-thyroid axis continuously exchange signals that shape metabolic pace, brain energy, and emotional tone. When cortisol remains elevated, thyroid signaling often quiets, and mood can flatten. Understanding this interaction offers a more complete and hopeful framework for interpreting persistent symptoms.
A 2023 cross-sectional study by Sinha and colleagues makes this interaction difficult to ignore. Their data show that cortisol levels are significantly elevated in hypothyroidism and closely correlated with the degree of thyroid dysfunction. [1] These findings invite a more curious and collaborative question. If sustained cortisol elevation can dampen thyroid signaling, what does that mean for brain energy, motivation, and emotional tone, and how might that understanding change the way care decisions are made?
To answer that, we need to follow cortisol’s influence from metabolism to mood.
Cortisol and the Thyroid: A Coordinated Downshift
Cortisol is essential for survival. It mobilizes glucose, supports blood pressure, and reallocates resources during stress. Thyroid hormones serve a different but complementary role. They set metabolic pace by regulating mitochondrial activity, oxygen consumption, and ATP turnover across nearly every tissue. [1]
When stress signals dominate, cortisol rises. When cortisol remains elevated, thyroid signaling often quiets. This is not accidental. It is adaptive.
In the study by Sinha et al., individuals with hypothyroidism had markedly higher serum cortisol levels than euthyroid controls. More importantly, cortisol levels tracked tightly with thyroid markers. Cortisol showed a strong positive correlation with TSH and a strong negative correlation with both T3 and T4. As thyroid hormone availability declined, cortisol rose. As TSH increased, cortisol followed. [1]
For individuals navigating symptoms and for clinicians guiding care, this pattern matters. It suggests that persistent symptoms may not reflect failure of treatment or effort, but a physiology still operating under constraint.
Why Cortisol Rises as Thyroid Function Falls
There are several potential mechanisms that help explain this relationship. Hypothyroidism slows metabolic clearance of cortisol, allowing cortisol to remain elevated for longer periods. At the same time, reduced thyroid hormone availability limits energy production. [1] The HPA axis may respond by increasing cortisol output to preserve glucose availability and cardiovascular stability.
But cortisol does not merely respond to thyroid dysfunction. It feeds back into the system. Elevated cortisol can suppress thyroid signaling at multiple levels of the HPT axis, further reducing metabolic output. [1] Over time, this creates a reinforcing loop. Lower thyroid hormone availability raises cortisol. Sustained cortisol elevation further dampens thyroid signaling.
From an energy perspective, this is cost containment. From a care perspective, it highlights the importance of context. Lab values tell part of the story. Lived experience tells another. Shared decision-making lives at the intersection of both.
Mood as an Energy-Dependent Process
Mood regulation is metabolically expensive. Neurotransmitter synthesis, synaptic signaling, and cortical network coordination require continuous ATP availability. When energy is constrained, emotional range and cognitive speed are often the first to downshift. [2]
Furthermore, psychological stress alters mitochondrial function and energy allocation in the brain, shaping emotional and cognitive states at a biological level. [2] When cortisol remains elevated, it signals the brain to prioritize survival physiology over restoration.
Thyroid hormones play a central role in this energetic landscape. They support mitochondrial efficiency, cerebral metabolic rate, and neural responsiveness. When cortisol suppresses thyroid signaling, brain energy availability narrows. [2]
For individuals experiencing low motivation or emotional flattening, this framing can be grounding. It shifts the narrative away from personal failure and toward physiology responding to sustained load.
How Sustained Cortisol Elevation Flattens Mood
Chronic cortisol elevation does not simply increase alertness. Over time, it reshapes brain function with prolonged HPA axis activation shifting neural systems toward energy conservation, reducing emotional flexibility and motivational drive. [3]
When cortisol remains high, thyroid hormone signaling is further constrained. Thyroid hormones normally support cognitive speed, emotional responsiveness, and reward sensitivity. When cortisol dampens thyroid signaling centrally and peripherally, these functions can downshift. [4] The result is not always overt sadness. More often, it presents as emotional flattening, motivation declines, pleasure feeling muted, slowed thinking, and a narrowing of the emotional range.
Recognizing this pattern allows both individuals and practitioners to ask different questions. Instead of asking why mood symptoms persist, the question becomes what signals the body is responding to, and how those signals might be shifted together.
Cortisol, Thyroid Function, and Mood: A Bidirectional Loop
The relationship between cortisol, thyroid hormones, and mood is not linear. Mokrani and colleagues describe how alterations in both the HPA and HPT axes are linked in depressive states, with cortisol excess and reduced thyroid signaling reinforcing one another. [5] In this framework, flattened mood is not a separate condition layered on top of endocrine dysfunction. It is part of the same adaptive response. When metabolic strain persists, physiology shifts toward endurance rather than engagement.
Korte and colleagues describe this as allostasis. Stress responses are beneficial in the short term but costly when sustained. [6] Emotional flattening may reflect an energy-conserving state under chronic load rather than a primary psychiatric disorder.
These perspectives carry hope. Adaptive systems are designed to respond, not remain stuck.
Rethinking Symptoms in Hypothyroidism
Thyroid dysfunction often reflects broader physiological context rather than an isolated gland issue. Cortisol signaling and brain energy availability are part of this picture. Considering cortisol alongside thyroid markers may clarify why symptoms such as low motivation, cognitive slowing, and flattened mood can persist despite improvements in thyroid labs, and where new opportunities for support may exist. [1]
When care decisions are made collaboratively, symptoms are not dismissed and labs are not treated as the sole authority. Instead, both are used to guide next steps. If cortisol remains elevated, thyroid hormone signaling at the tissue level, including in the brain, may remain constrained. The labs may improve, but the lived experience may lag behind.
Framed this way, persistent symptoms invite ongoing collaboration, using both objective data and lived experience to guide thoughtful, system-level support.
Physiology with Purpose
The endocrine system is adaptive, not broken. Elevated cortisol and dampened thyroid signaling may initially serve a protective role, but over time, the same adaptations can limit vitality and emotional range.
Understanding the role of cortisol in dampening thyroid function and flattening mood invites a more integrated and hopeful view of health. One that recognizes stress physiology, metabolic capacity, and emotional experience as interconnected systems that can be supported together.
The thyroid does not work alone. Cortisol does not act in isolation. Mood emerges from their balance. And with informed, shared decision making, that balance can shift.
Disclaimer:
The information provided is for educational purposes only. Consult your physician or healthcare practitioner if you have specific questions before instituting any changes in your daily lifestyle including changes in diet, exercise, and supplement use.
Allison Sayre, MSN, WHNP is a board-certified women’s health nurse practitioner with advanced expertise in hormonal health, integrative gynecology, and patient-centered care across the lifespan. She holds a Master of Science in Nursing and has served as both a clinical provider and educator in functional and conventional women’s health settings. At ARG, Allison contributes to medical education, clinical protocol development, and strategic content that supports the evolving needs of women's healthcare practitioners.
Corey Schuler, PhD, FNP, CNS has dedicated his career to advancing the science and clinical art of integrative medicine and serves as director of medical affairs for Allergy Research Group. He is a family nurse practitioner and practices holistic primary care at Synergy Family Physicians in White Bear Lake, Minnesota.